Background: Electronic cigarettes (e-cigarettes) were first introduced in the U.S. market in 2006, with the more recent evolution of "pod-mod" e-cigarettes such as JUUL introduced in 2015. Although marketed as a smoking cessation tool, e-cigarettes are rarely used for this purpose in youth. This review aims to synthesize the literature regarding e-cigarette use among youth, and provides a resource for clinicians, educators, and families that helps answer commonly asked questions about e-cigarettes. Methods: PubMed, Scopus, and PsycINFO search was performed using search terms "Electronic Nicotine Delivery Systems," "e cigarettes," "e-cigarettes," "electronic cigarettes," "vaping," "JUUL," "e-cigs," and "vape pens." Search results were filtered to only include those related to adolescents and young adults. Results: E-cigarette use among youth is common, with rates of use increasing from 1.5% in 2011 to 20.8% in 2018. Pod mod devices such as JUUL have gained favor among youth for their sleek design, user-friendly function, desirable flavors, and ability to be used discreetly in places where smoking is forbidden. Adolescents are often uninformed about the constituents of ecigarettes, and little is known about the long-term effects of e-cigarettes. Studies have suggested a "gateway" effect for combustible cigarettes and cannabis use. Conclusions: E-cigarette use is becoming increasingly common among youth, leading to a myriad of questions and concerns from providers, educators, and family members. More research is needed to determine the ultimate public health impact of e-cigarette use. The authors provide a summary table of frequently asked questions in order to help clarify these common concerns.

Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness.

Objectives Research using very low nicotine content (VLNC) cigarettes has shown that participants underreport use of non-study cigarettes. Biomarkers of nicotine exposure could be used to verify compliance with VLNC cigarettes. This study aimed to characterize biomarkers of exposure when participants exclusively use VLNC cigarettes. Methods 23 participants stayed in a hotel that permitted smoking for 5 days and 4 nights. They were provided 2 packs of VLNC cigarettes each day (0.4 mg of nicotine/g of tobacco; Spectrum cigarettes) and did not have access to other tobacco products. 24-hour urine samples were collected to assess exposure to nicotine and anatabine. Results After 4 days of exclusive use, the geometric means for urinary total cotinine, total nicotine equivalents (TNE), and anatabine were 1.13 nmol/ml (92% reduction), 3.17 nmol/ml (94% reduction) and 0.0031 nmol/ml (93% reduction). The population estimates of the 95th percentile of cotinine, TNE, and anatabine levels were 2.69, 6.41, and 0.0099 nmol/ml, respectively. Conclusions Study participants exclusively smoking 0.4 mg/g Spectrum cigarettes are unlikely to have biomarker values above these levels. The data presented here will be valuable to researchers conducting research on use of VLNC cigarettes.

Introduction Although nicotine is the primary reinforcing constituent in cigarettes, there is evidence that other constituents in cigarette smoke may interact with nicotine to reinforce smoking behavior. Methods The present experiments investigated whether a novel combination of these cigarette smoke constituents would increase nicotine self-administration in adult male rats. The constituents included five minor alkaloids (anabasine, nornicotine, cotinine, myosmine, and anatabine), two β-carbolines (harman and norharman), and acetaldehyde. All doses were indexed to be proportional to concentrations in cigarette smoke given a standard dose of nicotine used in rodent self-administration, or ten times higher than this standard. To model MAO inhibition seen in chronic smokers, some groups received separate injections of tranylcypromine prior to each self-administration session. Results Tranylcypromine increased low-dose nicotine self-administration independent of other smoke constituents, which had no effect on self-administration behavior. The effect of tranylcypromine was confirmed across a large range of reinforcement schedules. The effect of tranylcypromine on low-dose nicotine self-administration was observed regardless of whether the injection was delivered 1-hr or 23-hrs prior to the self-administration session, consistent with the interpretation that MAO inhibition was responsible for the increase in self-administration, instead of acute off-target effects. Conclusions These data suggest that this cocktail of constituents does not significantly alter the primary reinforcing effects of nicotine, but constituents that inhibit MAO may increase the primary reinforcing effects of nicotine, especially at low doses.

introduction: Food and Drug Administration-mandated product standards that drastically reduce nicotine content in cigarettes aim to decrease smoking and thus improve health outcomes for millions of U.S. smokers. Researchers have suggested that nicotine reduction should be implemented gradually, but a gradual nicotine reduction may shift the minimum level of nicotine required to reinforce behavior or may result in different levels of compensatory smoking behavior.

Aims To assess the impact of a reduction in the nicotine content of cigarettes on estimated consumption of reduced nicotine cigarettes and usual brand cigarettes at a variety of hypothetical prices. Design Double blind study with participants randomly assigned to receive cigarettes for six weeks that were either usual brand or an investigational cigarette with one of five nicotine contents. Setting Ten sites across the United States Participants 839 eligible adult smokers randomized from 2013 to 2014 Intervention and comparator Participants received their usual brand or an investigational cigarette with one of five nicotine contents: 15.8 (primary control), 5.2, 2.4, 1.3, or 0.4 mg/g. Measurements The Cigarette Purchase Task completed at Baseline and at Week 6 post-randomization visit. Findings Compared with normal nicotine content controls, the lowest nicotine content (0.4 mg/g) reduced the number of study cigarettes participants estimated they would smoke at a range of prices (mean reduction relative to 15.8 mg/g at a price of $4.00/pack: 9.5, 95% CI: 5.61,12.19). The lowest nicotine content also reduced the maximum amount of money allocated to study cigarettes and the price at which participants reported they would stop buying study cigarettes [median reduction relative to 15.8 mg/g (95% CI): $8.21 (4.27,12.15) per day and, and $0.44 (0.17,0.71) per cigarette, respectively]. A reduction in nicotine content to the lowest level also reduced the maximum amount of money allocated to usual brand cigarettes (median reduction relative to 15.8 mg/g: $4.39 per day, 95% CI: 1.88,6.90). Conclusions In current smokers, a reduction in nicotine content may reduce cigarette consumption, reduce the reinforcement value of cigarettes, and increase cessation if reduced-nicotine content cigarettes were the only cigarette available for purchase.

Log-survivor analyses of interresponse times suggest that the behavior of rats responding under single variable-interval schedules is organized into bouts (i.e., periods of engagement and disengagement). Attempts to generalize this analysis to the key pecking in pigeons, however, have failed to produce the characteristic broken-stick appearance typically obtained with rats. This failure may be due to a relatively low rate of reinforcement for engaging in alternative behavior experienced by pigeons. The present study tested this hypothesis by exposing four pigeons to concurrent schedules of reinforcement for key pecking, first without a changeover delay (COD) and then with a COD. In this arrangement, one of the concurrent options was treated as the target response and the rate of reinforcement for that option was manipulated across conditions. The other option provided explicit reinforcement for engaging in an alternative response (i.e., explicit reinforcement for disengaging from the target response). In the absence of a COD, log-survivor plots for three of the pigeons were approximately linear, thus providing no evidence that responding was organized into bouts. When a COD was present, plots were broken stick in appearance, indicating a bout structure had been generated in the pigeons' behavior. Both bout length and the rate of bout initiations were a function of differences in rate of reinforcement. These data suggest that behavior may become organized into bouts when contingencies create sufficiently long visits to both the target behavior and the extraneous behavior. Fits of a double-exponential model deviated systematically from the actual plots due to the presence of a plateau between the two limbs. An alternative, double-gamma, model was explored, and it provided a considerably better fit than did the double-exponential.

The Food and Drug Administration (FDA) has the authority to regulate cigarette smoke constituents, and a reduction in nicotine content might benefit public health by reducing the prevalence of smoking. Research suggests that cigarette smoke constituents that inhibit monoamine oxidase (MAO) may increase the reinforcing value of low doses of nicotine. The aim of the present experiments was to further characterize the impact of MAO inhibition on the primary reinforcing and reinforcement enhancing effects of nicotine in rats. In a series of experiments, rats responded for intravenous nicotine infusions or a moderately-reinforcing visual stimulus in daily 1-h sessions. Rats received pre-session injections of known MAO inhibitors. The results show that (1) tranylcypromine (TCP), a known MAO inhibitor, increases sensitivity to the primary reinforcing effects of nicotine, shifting the dose-response curve for nicotine to the left, (2) inhibition of MAO-A, but not MAO-B, increases low-dose nicotine self-administration, (3) partial MAO-A inhibition, to the degree observed in chronic cigarette smokers, also increases low-dose nicotine self-administration, and (4) TCP decreases the threshold nicotine dose required for reinforcement enhancement. The results of the present experiments suggest cigarette smoke constituents that inhibit MAO-A, in the range seen in chronic smokers, are likely to increase the primary reinforcing and reinforcement enhancing effects of low doses of nicotine. If the FDA reduces the nicotine content of cigarettes, then variability in constituents that inhibit MAO-A could impact smoking.