The purpose of this study was to determine whether an educational tobacco intervention impacted college students' perceptions relative to tobacco, self-efficacy, and perceived stress levels. The Health Belief Model (HBM) provided a theoretical framework to distinguish differences relative to tobacco between groups. Both the control (N=155) and intervention (N=184) group consisted of a convenience sample of students from a 2000-level health course. A pre- and post-test questionnaire was administered to both groups which included questions regarding demographics, tobacco use, HBM, self-efficacy, and perceived stress. Data analysis included frequency counts, confirmatory factor analysis, Cronbach's alpha, and two-way ANOVA. Two-way ANOVA results indicated statistically significant differences for the Health Belief Model questions (p=0.002) and self-efficacy items (p=0.03). No statistical significance was found regarding perceived stress. These findings provide evidence an educational tobacco intervention administered at the college level can have a significant impact on students. / by Kelley E. Rhoads. / Thesis (M.S.)--Florida Atlantic University, 2012. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2012. Mode of access: World Wide Web.

A major contributor to relapse following smoking cessation is nicotine craving triggered by environmental cues, such as the sight of a lighted cigarette. Therefore, three integrated functional neuroimaging studies were conducted to examine the biological mechanisms underling cue-elicited craving for cigarettes. (1) First, I examined the effect of smoking-related pictorial cues on neural activation hi brain regions of interest (ROI) associated with reward signalling using functional magnetic resonance imaging (fMRI). Voxel-wise analysis demonstrated that smokers, but not nonsmokers, demonstrated significant activation associated with smoking-related pictorial cues in the anterior cingulate cortex, orbitofrontal cortex, and ventral striatum. Upon ROI analysis of the ventral striatum including the nucleus accumbens (VS/NAc), smokers exhibited significantly greater VS/NAc activation than non-smokers. (2) Next, I examined whether pre-specifled serotonergic polymorphisms would affect binding potential (BP) to a serotonin (5-HT) receptor implicated in the behavioural sensitisation process to nicotine (5-HTiA receptor). Healthy volunteers who had undergone positron emission tomography (PET) with a 5-HTiA-specific ligand [ U C]WAY-100635 were genotyped for the 5-HT₁ A -1018 G>C and 5-HT transporter (5-HTT) 5-HTT gene-linked polymorphic region (5-HTTLPR) polymorphisms. Participants carrying the 5-HTTLPR S allele (SS or SL genotypes) demonstrated significantly lower global presynaptic and postsynaptic BP compared to subjects with LL genotypes. (3) Finally, I triangulated the two initial studies to examine whether pre-specified trait (5- HTTLPR genotype) and/or state (smoking vs. abstinence) variables would influence cueelicited activation of the VS/NAc. There was greater activation to smoking-related cues in the VS/NAc of smokers during the smoking condition than the abstinent condition and a significant correlation between tobacco craving and VS/NAc activation in the smoking condition. The 5-HTTLPR polymorphism was not associated with VS/NAc activation. Power calculations are presented as the basis for future examination of genetic hypotheses. These data have implications for the ultimate goal of enhancing the efficacy of smoking cessation pharmacotherapy.

BACKGROUND: Tobacco is the most commonly used addictive substance among adolescents, according to the ESPAD study, and is often the first psychoactive substance to try out in life. However, the risks associated with the use of tobacco at the young age are not negligible. In the Ambulance for children and adolescents addictology Clinics of addictology, where attend adolescents with various addictological and psychological problems, no research regarding the use of nicotine has been carried out. AIMS: The aim of the work is to map and describe the patterns of use of nicotine and motivation for use among children and adolescents with problems with addictive substances or in the field of non-addictive addictions. Another aim of the work is to find the degree of physical dependence on nicotine in the target group of respondents. METHODS: Data were collected using a questionnaire, which included Fagerström's nicotine addiction test for adolescents to assess the degree of physical nicotine dependence in respondents. The questionnaire was submitted in paper form to the clients of the Ambulance for children and adolescents addictology of the Clinic of addictology. The research sample was selected by deliberate selection through the institution. Descriptive statistics were used to evaluate the results and...

Cigarette smoking is an addictive behavior. There are two learned emotional responses to smoking that may be particularly important for promoting addiction to smoking: the pleasure obtained from the airway sensory effects of smoking (airway sensory pleasure) and the urge to smoke that is elicited by environmental smoking cues (cue-induced urge). The ventromedial prefrontal cortex (VMPFC) has been implicated in a variety of learned emotional and motivational responses to drug-associated sensory cues. This project set out to address the role of the VMPFC and related areas in airway sensory pleasure and cue-induced urge, as well as the role of this region in promoting smoking behavior in real life, by examining the effects of focal lesions within the VMPFC and related areas in human cigarette smokers. It was found that lesions of the VMPFC itself were associated with a marked impairment of cue-induced urge in the laboratory, which was paralleled by a reported reduction in the difficulty of abstaining from smoking in real life. At the same time, VMPFC lesions led to a relative sparing of airway sensory pleasure in the laboratory, which was paralleled by no change in the enjoyment from smoking in real life. In addition, it was found that VMPFC lesions were not associated with changes in real-life measures of smoking dependence. It was found that lesions of the insula, a region that is functionally related to the VMPFC, were associated with an ability to quit smoking easily, immediately, without relapses and without a lasting urge to smoke. However, among patients with insula lesions who continued to smoke after lesion onset, there were no appreciable impairments of airway sensory pleasure or cue-induced urge. The results suggest that, while VMPFC lesions may disrupt cue-induced urges, they do not disrupt dependence upon smoking. This may be because VMPFC lesions spare more implicit motivational processes, such as "habits" and "incentive salience," that can drive smoking behavior in the absence of a conscious desire to smoke. The results also suggest that the insula functions in psychological processes that may contribute to the difficulty of quitting smoking.

Electronic nicotine delivery systems emerged during the 2010s as a novel way to consume (i.e., vape) nicotine. Public health authorities became concerned that vaping could cause nicotine-naïve youth to begin using tobacco products and that a new generation of youth could become tobacco-dependent. Though millions of youth have vaped, authorities' fears about a new generation of youth tobacco dependence has not materialized. A more recent concern is nicotine vaping’s potential effects on cannabis use and the use of other substances. An increase in cannabis use among some adolescent groups and young adults could be because of nicotine vaping’s rise. Additionally, cannabis can be vaped, so transitioning from nicotine vaping to cannabis vaping may be easier than transitioning from nicotine vaping to other forms of cannabis use. Furthermore, nicotine product use was historically associated with later use of cannabis and other substances; this trend may be renewed with the advent of nicotine vaping. To date, most studies on the associations between nicotine vaping and cannabis/other substance use are cross-sectional, so more longitudinal evidence is needed. If evidence suggests that nicotine vaping does affect the use of cannabis and other substances, specifying a mechanism would help with developing potential interventions and with testing the validity of total effects. The overarching goal of this dissertation is to advance evidence of nicotine vaping's potential harmful effects on youth and young adults, which could be used to support interventions aimed at reducing the burden of nicotine vaping's outcomes. First, I conducted a systematic review in which I examined the extent to which confounding, measurement errors, and loss to follow-up could alternatively explain reported longitudinal effects of nicotine vaping on cannabis use or other substance use. I also identified studies that tested effect modification and mediation. This systematic review revealed that nicotine vaping likely increases the risk of subsequent cannabis use and other substance use for up to 24 months. It also revealed that some studies evaluated effect measure modification, while no study assessed mechanisms. These observations suggest that future studies should assess long-term effects on initiation and evaluate potential mechanisms. Second, I evaluated whether nicotine vaping affected the initiation of cannabis and other substances over a six-year period among adolescents as they age into adulthood. Results suggested that nicotine vaping had harmful effects on both outcomes over the six-year period. I also found evidence that nicotine vaping's harmful effects in later years appeared stronger than in earlier years; the absence of age effects suggest the absence of cohort effects. Furthermore, I found that effects appeared stronger among individuals who had a history of non-vaping tobacco product use than among individuals without a history of non-vaping tobacco product use, suggesting that tobacco use is key to nicotine vaping's harms. Finally, I evaluated possible mechanisms of the effects based on a theory that I developed from prior empirical literature and behavioral theory. I posited that nicotine vaping caused deviant peer affiliation, which caused conduct problems and subsequently, the outcomes. I found no evidence that three conduct problems (considered together) were mechanisms of the effects. Future studies of mechanisms can reveal potential intervention targets, lead to studies of other potential mechanisms, and help test the validity of total effects. This dissertation achieved its goal of advancing evidence that nicotine vaping may harm youth and young adults. Public health bodies tasked with addressing potential public health concerns about nicotine vaping products should consider evidence from this dissertation.

Tobacco smoking has consistently been the leading cause of preventable diseases and premature deaths. Currently, pharmacological interventions have only shown limited smoking cessation efficacy and sometimes are associated with severe side effects. As an alternative, nicotine vaccines have emerged as a promising strategy to combating nicotine addiction. However, conventional conjugate nicotine vaccines have shown limited ability to induce a sufficiently strong immune response due to their intrinsic shortfalls. In this study, a lipid-poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based next-generation nicotine vaccine has been developed to overcome the drawbacks of conjugate nicotine vaccines. Also, the influence of multiple factors, including nanoparticle size, hapten density, hapten localization, carrier protein, and molecular adjuvants, on its immunogenicity has been investigated. Results indicated that all these studied factors significantly affected the immunological efficacy of the nicotine nanovaccine. First, 100 nm nanovaccine was found to elicit a significantly higher anti-nicotine antibody titer than the 500 nm nanovaccine. Secondly, the high-density nanovaccine exhibited a better immunological efficacy than the low- and medium-density counterparts. Thirdly, the nanovaccine with hapten localized on both carrier protein and nanoparticle surface induced a significantly higher anti-nicotine antibody titer and had a considerably better ability to block nicotine from entering the brain of mice than the nanovaccines with hapten localized only on carrier protein or nanoparticle surface. Fourthly, the nanovaccines carrying cross reactive materials 197 (CRM197) or tetanus toxoid (TT) showed a better immunological efficacy than the nanovaccines using keyhole limpet hemocyanin (KLH) or KLH subunit as carrier proteins. Finally, the co-delivery of monophosphoryl lipid A (MPLA) and Resiquimod (R848) achieved a considerably higher antibody titer and brain nicotine reduction than only using MPLA or R848 alone as adjuvants. Collectively, the findings from this study may lead to a better understanding of the impact of multiple factors on the immunological efficacy of the hybrid nanoparticle-based nicotine nanovaccine. The findings may also provide significant guidance for the development of other drug abuse and nanoparticle-based vaccines. In addition, the optimized lipid-PLGA hybrid nanoparticle-based nicotine nanovaccine obtained by modulating the studied factors can be a promising candidate as the next-generation nicotine vaccine for treating nicotine addiction. / PHD

Nicotine titration was studied in cigarette smokers not interested in cutting down or quitting smoking. Forty smokers were classified as high nicotine dependent (n=20) and low nicotine dependent (n=20) using a validated tolerance questionnaire. Subjects were randomized into baseline (n=10) or nicotine fade conditions (n=10) within their dependency group. Subjects in the baseline conditions smoked their preferred brand of cigarette throughout the experiment. Smokers in the fade conditions switched to a reduced nicotine brand in the latter half of the procedure. Multiple in vivo and in vitro measures of smoking rate and topography were collected over a four day period. Based on analyses of these data, it was concluded that no compensatory changes in smoking behavior occurred that were clearly attributable to nicotine titration. It was found that smokers classified as high nicotine dependent smoked more intensively that low dependent smokers. The implications of these findings given the design and experimental controls employed in this experiment are discussed, and directions for future research explored. / M.S.

Nicotine Addiction is a chronic relapsing disorder. Relapse risk persists despite years of abstinence. Drug-associated cues have been demonstrated to induce craving and provoke relapse. Surprisingly, in human smokers, craving for nicotine increases or “incubates” with longer abstinence durations, a phenomenon that may explain persistent relapse liability. This incubation phenomenon also presents in animals trained to intravenously self-administer nicotine though the underlying mechanisms are unclear. Two proteins, ERK (Extra-cellular signal Regulated Kinase) and CREB (cAMP Response Element Binding protein) play important roles in learning, memory, and numerous aspects of drug addiction. We therefore examined whether changes in these proteins are associated with incubation of craving for nicotine in rats. We found increased nicotine-seeking behaviour after 14 days of abstinence (compared to 1 day) along with elevated ERK and CREB activity in the Accumbens brain region suggesting that these proteins may be involved in the incubation phenomenon.

Nicotine Addiction is a chronic relapsing disorder. Relapse risk persists despite years of abstinence. Drug-associated cues have been demonstrated to induce craving and provoke relapse. Surprisingly, in human smokers, craving for nicotine increases or “incubates” with longer abstinence durations, a phenomenon that may explain persistent relapse liability. This incubation phenomenon also presents in animals trained to intravenously self-administer nicotine though the underlying mechanisms are unclear. Two proteins, ERK (Extra-cellular signal Regulated Kinase) and CREB (cAMP Response Element Binding protein) play important roles in learning, memory, and numerous aspects of drug addiction. We therefore examined whether changes in these proteins are associated with incubation of craving for nicotine in rats. We found increased nicotine-seeking behaviour after 14 days of abstinence (compared to 1 day) along with elevated ERK and CREB activity in the Accumbens brain region suggesting that these proteins may be involved in the incubation phenomenon.

The CHRNA5/A3/B4 genomic cluster encodes for the alpha5, alpha3 and beta4 subunits of the nicotinic acetylcholine receptors (nAChRs). Human genetic studies have revealed a significant association of variants in this genomic region with nicotine dependence. However, the mechanisms through which overexpression of these three subunits may influence smoking-related behaviours is not understood. To gain insight in the possible mechanisms, we used a BAC transgenic mouse model overexpressing this cluster containing the three genes together with their transcriptional regulatory elements. We found that overexpression of the cluster: i) increases sensitivity to the pharmacological effects of nicotine; ii) modifies particular cognitive domains associated to drug addiction and hippocampal neuronal complexity and synaptic plasticity; and iii) shifts the rewarding and aversive properties of nicotine and the manifestation of nicotine-withdrawal syndrome. Our study suggests that the genomic cluster CHRNA5/A3/B4 contributes to genetic vulnerability to nicotine addiction and promotes smoking-related behaviours possibly through hippocampal plasticity changes. / El cluster genòmic CHRNA5/A3/B4 codifica per les subunitats alfa5, alfa3 i beta4 dels receptors d’acetilcolina (nAChRs). Estudis de genètica humana han revelat que variants en aquesta regió genòmica estan significativament associats a la dependencia a nicotina. Malauradament, els mecanismes pels quals la sobreexpressió d’aquestes tres subunitats influencia comportaments relacionats amb el consum de tabac no són del tot coneguts. Per tal d’entendre els possibles mecanismes, hem utilitzat un model de ratolí transgènic que sobreexpressa aquest cluster amb els tres gens i les seus elements de regulació transcripcional. Hem trobat que la sobreexpressió del cluster: i) incrementa la sensibilitat als efectes farmacològics de la nicotina; ii) modifica determinats dominis cognitius associats a l’addicció a droges i la complexitat neuronal i plasticitat sinàpica de l’hipocamp; a més a més iii) canvia les propietats de recompensa i aversió de la nicotina i la manifestació del síndrome d’abstinència. El nostre estudi suggereix que el cluster genòmic CHRNA5/A3/B4 contribueix a la vulnerabilitat genètica a l’adicció a la nicotina i promou comportaments relacionats amb el consum de tabac possiblement a través de canvis de plasticitiat a l’hipocamp.