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INTRODUCTION: There remains a paucity of research quantifying alcohol’s effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8 g/kg). As drinkers with AUD frequently engage in very heavy drinking (8-10 drinks/occasion), doses of ≤0.8 g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2 g/kg) to non-treatment seeking AUD participants. METHODS: Sixty-one young-adult AUD drinkers enrolled in the Chicago Social Drinking Project and completed three laboratory sessions at which they consumed a beverage with 1.2 g/kg, 0.8 g/kg, and 0.0 g/kg alcohol. Physiological responses (vital signs, nausea and vomiting, breath alcohol concentrations (BrAC)) were monitored throughout the sessions. After each session, participants completed a next-day survey of substance use, engagement in risky behaviors, and related consequences. RESULTS: Overall, the sample demonstrated good compliance with study procedures; 93% of participants adhered to pre-session alcohol abstinence requirements (indicated by BrAC

Aim The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. Methods The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. Results Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. Conclusions Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches.

RATIONALE: Electronic nicotine delivery systems (ENDS or e-cigarettes) share salient features of combustible smoking, such as inhalation and exhalation behaviors, and evidence indicates that first and second-generation ENDS generalize as smoking cues. The present study examined whether newer, tank-based third-generation ENDS (“mods”) also evoke smoking urges, and whether enhancing the visibility of exhaled aerosol clouds - by increasing the e-liquid vegetable glycerin (VG) content - strengthens the cue salience of ENDS. OBJECTIVES: The objective was to assess the role of exhaled aerosol clouds on ENDS cue potency using a standardized laboratory paradigm designed to mimic real-world exposures METHODS: Using a mixed design, young adult smokers (n=50; mean age 26.5 yrs; ≥5 cigarettes/day) observed a study confederate drinking bottled water (control cue) and vaping an ENDS mod containing e-liquid with either high (73%) or low (0%) VG. Participants completed the Brief Questionnaire on Smoking Urges (BQSU) and visual analog scales (VAS) assessing cigarette and e-cigarette desire pre- and post-cue exposure. RESULTS: Increasing the e-liquid content of VG enhanced the size and visibility of the exhaled aerosol clouds and evoked a greater increase in smoking desire and a more sustained increase in e-cigarette desire relative to the low VG cue. Both cues elicited increases in smoking urges. These results remained after controlling for sex, prior ENDS experience, recent smoking behavior, and menthol preference. CONCLUSIONS: Observation of tank-based ENDS use generalizes as a smoking cue and its cue salience is strengthened by increasing the e-liquid content of VG to enhance the visibility of the exhaled aerosol cloud.

BackgroundExposure to the use of first, second and third generations of electronic cigarettes (e-cigarettes) elicits the desire to vape and smoke among observers, as well as facilitates smoking behaviour. Given the rapid rise in the popularity of the pod mod JUUL, we examined whether observing the use of this device would elicit similar responses in smokers. Exploratory analyses were also conducted to determine whether JUUL can act as a smoking cue for former smokers.MethodsThe sample consisted of 82 young adult participants (62 current smokers and 20 former smokers approximately 1 year smoke free). The study examined their response to observing use of bottled water (control cue) and JUUL (active cue) in a controlled laboratory paradigm. Both cues were delivered by a trained study confederate under the guise of a social interaction task, and participants completed mood and desire and urge surveys precue and postcue exposures.ResultsIn current smokers, exposure to the JUUL cue increased smoking urge and desire for a cigarette, mod/vape pen and JUUL, and two-thirds chose to smoke in the behavioural analogue task. In former smokers, the JUUL cue evoked modest and transient increases in desire for a cigarette and JUUL.ConclusionsThe use of JUUL affects the user and elicits responses in observers; this study is the first to demonstrate that exposure to JUUL use may act as a smoking cue and exposure to JUUL use may affect tobacco control efforts.

Introduction Passive exposure to the use of electronic nicotine delivery systems (ENDS or e-cigarettes) has been shown to generalize as a smoking cue. As young adult women in particular are increasingly targeted by ENDS distributors, the present study examined whether passive exposure to the use of a female-marketed ENDS product selectively enhanced smoking urge, cigarette and e-cigarette desire, and smoking behavior among women (vs men) smokers. Methods Using a mixed design, young adult smokers (n = 64; mean age 28.2 yrs.; ≥5 cigarettes/day) observed a study confederate drink bottled water (control cue) and then vape a female-marketed tank-based ENDS (active cue). Main measures were the Brief Questionnaire of Smoking Urges (BQSU) and visual analog scales (VAS) for cigarette and e-cigarette desire pre- and post-cue exposure, followed by a smoking latency task. Results Compared to the control cue, the female-marketed ENDS cue increased smoking urge and desire for cigarettes and e-cigarettes to a similar extent in women and men. It also affected subsequent smoking behavior similarly between the sexes, with 68% of men and 58% of women opting to smoke (vs. obtaining monetary reinforcers). Conclusions Both women and men were sensitive to the use of the female-marketed ENDS as a smoking cue. Consistent with prior work by our group, findings demonstrate the cue salience of ENDS, which may be attributable to the aspects of vaping that resemble traditional smoking (e.g. hand-to-mouth and inhalation and exhalation behaviors).

Background Preclinical and clinical evidence suggest that the neuropeptide oxytocin may be of value in treating alcohol use disorder, by either reducing the rewarding effects of alcohol or reducing negative affect induced by alcohol withdrawal. However, the effect of a single dose of oxytocin on subjective and psychomotor responses to alcohol in social drinkers is not known. Methods This study examined the effect of intranasal oxytocin on subjective, behavioral, and physiological responses to a moderate dose of alcohol (0.8 g/kg) in young adult social drinkers. Participants (N = 35) completed 2 study sessions at which they consumed beverages containing alcohol (ALC; N = 20) or placebo (NoALC; N = 15) in combination with intranasal oxytocin (40 IU with a 20 IU booster) or placebo. They received oxytocin at one session and placebo at the other session (order counterbalanced) 20 minutes before consuming beverages. Subjective mood and drug effects ratings, heart rate and blood pressure, and 4 behavioral tasks (flanker task, digit span, go/no-go, and pursuit rotor) were the primary outcome measures. Results ALC produced its expected subjective and behavioral effects; including feeling intoxicated and impaired performance on the digit span and go/no-go tasks. Oxytocin alone had no significant subjective or physiological effects, and it did not affect responses to alcohol on any measure. Conclusions We can conclude that, under these conditions, a single dose of intranasal oxytocin does not alter the effects of acute alcohol in healthy young adult social drinkers. Further research is needed to determine whether oxytocin alters responses to alcohol under different conditions, and to determine its potential as an aid in treatment for substance use disorders.