Melissa D. Blank

Nicotine Interactions with Low-Dose Alcohol: Pharmacological Influences on Smoking and Drinking Motivation

An extensive literature documents a close association between cigarette and alcohol use. The joint pharmacological effects of alcohol and nicotine on smoking and drinking motivation may help explain this relationship. This experiment was designed to test the separate and combined pharmacological effects of nicotine and a low dose of alcohol (equivalent to 1-2 standard drinks) on substance use motivation using a double-blind and fully crossed within-subjects design. Participants (N = 87) with a wide range of smoking and drinking patterns completed 4 counterbalanced experimental sessions during which they consumed an alcohol (male: 0.3g/kg; female: 0.27g/kg) or placebo beverage and smoked a nicotine (.6 mg) or placebo cigarette. Outcome measures assessed the impact of drug administration (alcohol or nicotine) on craving to smoke, craving to drink, affect, and liking of the beverage and cigarette. Results indicated that combined administration produced higher cravings to smoke for the entire sample, as well as higher cravings to drink among women and lighter drinkers. Heavier users of either alcohol or cigarettes also exhibited enhanced sensitivity to the effects of either drug in isolation. Separate, but not interactive, effects of alcohol and nicotine on mood were observed as well as both same-drug and cross-drug effects on beverage and cigarette liking. Together, these findings support the notion that the interactive pharmacological effects of nicotine and low doses of alcohol play an important role in motivating contemporaneous use and suggest roles for cross-reinforcement and cross-tolerance in the development and maintenance of alcohol and nicotine use and dependence.

An Observational Study of Group Waterpipe Use in a Natural Environment

INTRODUCTION To date research on tobacco smoking with a waterpipe (hookah, narghile, and shisha) has focused primarily on the individual user in a laboratory setting. Yet, waterpipe tobacco smoking is often a social practice that occurs in cafés, homes, and other natural settings. This observational study examined the behavior of waterpipe tobacco smokers and the social and contextual features of waterpipe use among groups in their natural environment. METHODS Trained observers visited urban waterpipe cafés on multiple occasions during an 8-month period. Observations of 241 individual users in naturally formed groups were made on smoking topography (puff frequency, duration, and interpuff interval [IPI]) and engagement in other activities (e.g., food and drink consumption, other tobacco use, and media viewing). RESULTS Most users were male in group sizes of 3-4 persons, on average, and each table had 1 waterpipe, on average. The predominant social features during observational periods were conversation and nonalcoholic drinking. Greater puff number was associated with smaller group sizes and more waterpipes per group, while longer IPIs were associated with larger group sizes and fewer waterpipes per group. Additionally, greater puff frequency was observed during media viewing and in the absence of other tobacco use. CONCLUSIONS Overall, the results suggest that waterpipe smoking behavior is affected by group size and by certain social activities. Discussion focuses on how these findings enhance our understanding of factors that may influence exposure to waterpipe tobacco smoke toxicants in naturalistic environments.

The role of caffeine in the alcohol consumption behaviors of college students

BACKGROUND Evidence suggests that alcohol mixed with caffeine in any form may spur risky drinking behavior among young adults; however, most studies have only examined drinking behavior related to alcohol mixed with energy drinks (AmEDs) compared with alcohol alone. This survey assessed the consumption patterns and reasons for use of alcohol mixed with any caffeinated beverages (alcohol-caffeine) versus alcohol-only beverages among current users. METHODS Students (N = 1174) at a large, urban university completed a Web-based survey in October-December of 2010. Predictors of alcohol-caffeine use versus alcohol-only use were examined, as were drinking characteristics and reasons for alcohol-caffeine consumption as a function of type of alcohol-caffeine beverage usually consumed. RESULTS Past-30-day prevalence was 34% for any alcohol-caffeine beverages and 36% for alcohol-only. The most frequent alcohol-caffeine beverages usually consumed were manufactured ready-to-drink AmED products (no longer sold in the United States; 50.3%), followed by self-mixed alcoholic beverages containing caffeinated sodas (26.4%) and energy drinks (18.5%). Users of alcohol-caffeine displayed a riskier drinking profile than alcohol-only users; however, there were few differences in overall alcohol drinking behaviors between consumers of AmEDs (manufactured or self-mixed) versus other caffeinated alcoholic beverages (e.g., alcohol mixed with caffeinated sodas). CONCLUSIONS Although alcohol-caffeine consumption was associated with heavier drinking characteristics compared with alcohol-only consumption, overall alcohol consumption patterns were similar between users of various alcohol-caffeine combinations. Future examinations should assess alcohol in combination with a variety of caffeine sources to determine whether energy drinks present a unique risk.

Comparison of Puff Topography, Toxicant Exposure, and Subjective Effects in Low- and High-Frequency Waterpipe Users: A Double-Blind, Placebo-Control Study

INTRODUCTION Clinical laboratory work among intermittent and daily waterpipe tobacco smokers has revealed significant risks for tobacco dependence and disease associated with waterpipe tobacco smoking (WTS). No studies have compared these groups directly. This study examined whether WTS frequency was associated with differential puff topography, toxicant exposure, and subjective response using a placebo-control design. METHODS Eighty participants reporting WTS of 2-5 episodes (LOW; n = 63) or ≥20 episodes (HIGH; n = 17) per month for ≥6 months completed 2 double-blind, counterbalanced 2-hr sessions that were preceded by ≥12hr of tobacco abstinence. Sessions differed by product smoked ad libitum for 45+ min: preferred brand/flavor of waterpipe tobacco (active) or a flavor-matched tobacco-free waterpipe product (placebo). Outcomes included puff topography, plasma nicotine, carboxyhemoglobin (COHb), and subjective response. RESULTS HIGH users had more puffs, shorter inter-puff-intervals, and a higher total puff volume for placebo relative to active, as well as relative to LOW users during placebo. Plasma nicotine concentrations increased when smoking active (but not placebo) with no significant differences between groups at 25min post-product administration. COHb increased significantly during all conditions; the largest increase was for HIGH users when smoking placebo. There was some evidence of higher baseline scores for nicotine/tobacco nicotine abstinence symptomology. CONCLUSIONS Higher frequency waterpipe users may be more sensitive to the effects of waterpipe smoke nicotine content. Among HIGH users, higher baseline nicotine/tobacco abstinence symptoms may indicate greater nicotine dependence. These data support continued surveillance of WTS and development of dependence measures specific to this product.

Commentary on Brose et al. (2015): Protecting individual and public health by regulating electronic cigarette nicotine delivery

Brose and colleagues [1] used a national data set from Great Britain to demonstrate that, in current tobacco cigarette smokers, daily but not non-daily electronic cigarette (e-cig) use shows a significant association with increased tobacco smoking cessation attempts and reductions in smoking behavior. However, e-cig use was not shown in this study to be associated significantly with tobacco smoking cessation. Taken together, this new study [1] and the extant literature (e.g. [2, 3]) provide little empirical support for the contention that e-cig use leads reliably to smoking cessation for the majority of users. Tobacco cigarette smokers self-administer the stimulant drug nicotine with every puff that they inhale, and most of them are dependent on the drug [4]. This dependence makes cessation difficult, in part because of an aversive abstinence syndrome that occurs during a cessation attempt (e.g. [5]). Nicotine replacement medications act by delivering nicotine to the user and thus suppressing at least some aversive abstinence symptoms: the more nicotine, the greater the symptom suppression (e.g. [6]). E-cigs are not marketed as medications in many countries, but are a class of products that use an electric heater to aerosolize a liquid that usually contains some combination of propylene glycol, vegetable glycerin, flavorants and nicotine. Despite not being marketed as medications, many smokers are attempting to quit tobacco cigarettes by using e-cigs daily; however, there is little information regarding the long-term health risks associated with daily e-cig use. Putting aside that concern, if daily e-cig use is to lead to smoking cessation for the majority of users, then e-cigs will probably need to deliver nicotine in doses necessary to suppress abstinence symptoms as effectively as a tobacco cigarette. Unfortunately, there is wide variability in e-cig nicotine delivery: 10 puffs from an e-cig may, for example [7], or may not [8], result in reliable nicotine delivery to the user’s blood. Differences across studies can be explained by a combination of factors, including characteristics of the e-cig device and liquid, as well as user behavior [9]. Those e-cig device/liquid combinations that are most likely to lead to smoking cessation may well be those that approximate the nicotine delivery profile of a tobacco cigarette (e.g. [10]). Strangely, e-cigs that are far less effective at delivering nicotine continue to be marketed to smokers. For instance, 50 puffs from either of two Blu e-cig (Lorillard, Inc., Greensboro, NC, USA) models that are currently available on the US market deliver 23–53% less nicotine to the user relative to approximately 10 puffs from a conventional tobacco cigarette [11], yet Blu e-cig brands are rated as the most popular among US young adults [12]. Perhaps relatedly, more than 80% of all US televised e-cig advertisements geared toward youth and young adults were for Blu e-cigs [13], and 90% of all US advertising expenditures for e-cig brands have been for Blu E e-cigs [14]. The fact that some e-cigs that are advertised to youth and young adults actively also deliver very little nicotine is reminiscent of so-called ‘starter products’ common in the smokeless tobacco arena [15]. Starter products allow nicotine-naive users to self-administer low doses of nicotine without experiencing drug-mediated adverse side effects and then, as tolerance develops, these users can ‘graduate’ to products that deliver increasing doses of the drug (e.g. [15]). Public health policy-makers may want to recall this industry strategy when considering regulatory action regarding e-cigs. Further complicating this issue is that at least 466 distinct brands of e-cigs are marketed currently [16], some by major tobacco companies. Tobacco companies in particular may be interested in smokers who purchase an e-cig as part of a smoking cessation strategy but, as Brose et al.’s [1] data suggest, ultimately do not quit smoking, perhaps because the e-cig they bought underperforms a tobacco cigarette in terms of nicotine delivery to the user. Under this scenario, the tobacco company that sells the under-performing product profits from sales of e-cigs and tobacco cigarettes, while the smoker who purchased the under-performing product in addition to tobacco cigarettes continues to be at risk for tobacco-caused disease and death. Much has been written about the potential for e-cigs to provide public health benefit through a dramatic reduction in tobacco cigarette smoking (e.g. [17]). This potential benefit may require science-based regulatory intervention to ensure that e-cigs deliver nicotine effectively to cigarette smokers, while avoiding e-cig-induced nicotine dependence in non-smokers via the starter product strategy. Also, some e-cig device/liquid combinations on the market today may deliver nicotine more effectively than the highly addictive tobacco cigarette [18]; there is no clear public health rationale for such products, and regulation can help to limit their availability. Relevant foci for regulatory intervention that address drug delivery include product characteristics [9] and nicotine flux [19]. Without meaningful, science-based regulation, there may be many future opportunities to report, as do Brose et al. [1], that e-cigs are not effective tools for helping the majority of smokers to quit using lethal tobacco cigarettes.

Effects of intravenous nicotine on prepulse inhibition in smokers and non-smokers: relationship with familial smoking

RationaleThe 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.ObjectivesThe 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.MethodsThe 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.ResultsAnalyses 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.ConclusionsThese data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk.

Acute effects of snus in never-tobacco users: a pilot study.

ABSTRACT Background: Snus tobacco characteristics may attract non-tobacco users, including relatively low, but pharmacologically active, doses of nicotine. Lower nicotine doses may limit adverse drug effects while also producing a physiologically active response. Objectives: This pilot study is the first to profile the acute effects of snus on physiological and subjective assessments in a sample of never-tobacco users. Methods: Eleven never-tobacco users (five women; <100 uses/lifetime) were recruited from the community via university-approved advertisements. Using a within-subject design, participants consumed six pouches in ascending dose order (0, 1.6, 3.2, 4.8, 6.4, and 8.0 mg nicotine) within one session. The start of each snus bout was separated by 45 minutes, and pre- and post-pouch assessments included ratings of drug effects and physiological response. Results: The average heart rate and systolic blood pressure increased significantly from pre- to post-pouch use as a function of dose, though these increases were reliable for 8.0 mg nicotine only (p < .05). Collapsed across time, diastolic blood pressure was significantly higher for 8.0 mg nicotine than for all other doses (p < .05). Subjective ratings for “excessive salivation” and “satisfying” increased significantly from pre- to post-pouch use (p < .05), independent of dose. Conclusion: Significant increases in physiological response at some doses suggest that users were exposed to pharmacologically active doses of nicotine. The lack of reliable subjective effects may be the product of the dosing regimen or the relatively small sample size. Findings highlight the need for identification of doses of snus that may promote abuse among naïve users.

A pilot investigation of the effect of electronic cigarettes on smoking behavior among opioid-dependent smokers

INTRODUCTION Compared to the general population, smoking rates are 2-4 times higher among individuals with opioid use disorders (OUDs). These smokers also have poor long-term cessation rates, even with pharmacotherapy or other interventions. Low success rates with traditional approaches may prompt smokers with OUDs to try more novel products like electronic cigarettes (ECIGs). This pilot study was designed to examine the feasibility, acceptability, and effect of ECIGs on smoking behavior among smokers with OUD. METHODS Participants (N = 25) were daily smokers receiving buprenorphine/naloxone for OUD at an outpatient clinic. They were randomized to use a second-generation ECIG (0 or 18 ng/ml nicotine) ad libitum for two weeks while completing assessments via text messaging daily, and also via in-person visits at baseline, end of the two-week intervention, and a 4-week follow-up. RESULTS Feasibility was evidenced by high enrollment (93.9%) and retention (70.9%) rates. ECIG adherence was relatively high as measured by self-report (80.6% active, 91.7% placebo), while the average volume of liquid used per week was low (~3 ml). Both ECIG doses produced reductions in self-reported cigarettes per day that were not supported by average carbon monoxide levels. Biologically-confirmed smoking abstinence was observed in 8% of participants. CONCLUSIONS Preliminary results suggest that smokers with OUD are interested in using ECIGs, but their adherence may be less than ideal. Poor medication adherence rates are often observed in this disparate population, and future work should consider the use of other ECIG device types and a combination of methods to verify and quantify ECIG use.

Cigarette smoking duration mediates the association between future thinking and norepinephrine level

Fixating on the present moment rather than considering future consequences of behavior is considered to be a hallmark of drug addiction. As an example, cigarette smokers devalue delayed consequences to a greater extent than nonsmokers, and former smokers devalue delayed consequences more than nonsmokers, but less than current smokers. Further, cigarette smokers have higher norepinephrine levels than nonsmokers, which is indicative of poor future health outcomes. It is unclear how duration of cigarette smoking may impact these associations. The current secondary analysis of publicly available data investigated whether extent of future thinking is associated with smoking duration, as well as norepinephrine level, in a large national US sample (N = 985) of current, former, and never smokers. Individuals scoring lower on future thinking tended to smoke for longer durations and had higher norepinephrine levels relative to individuals scoring higher on future thinking. In addition, duration of cigarette abstinence interacted significantly with future thinking and smoking duration for former smokers. Specifically, the mediation relationship between future thinking, smoking duration, and norepinephrine level for former smokers was strongest at shorter durations of cigarette abstinence and decreased as a function of increasing duration of cigarette abstinence. Overall, results from this study suggest the potential importance of implementing smoking cessation treatments as early as possible for smokers and support future thinking as a potential therapeutic target for smoking cessation treatment.