Nicotine Intake Research Articles

Rodent models for nicotine withdrawal.

Animal models are critical to improve our understanding of the neuronal mechanisms underlying nicotine withdrawal. Nicotine dependence in rodents can be established by repeated nicotine injections, chronic nicotine infusion via osmotic minipumps, oral nicotine intake, tobacco smoke exposure, nicotine vapor exposure, and e-cigarette aerosol exposure. The time course of nicotine withdrawal symptoms associated with these methods has not been reviewed in the literature. The goal of this review is to discuss nicotine withdrawal symptoms associated with the cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure in rats and mice. Furthermore, age and sex differences in nicotine withdrawal symptoms are reviewed. Cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure leads to nicotine withdrawal symptoms such as somatic withdrawal signs, changes in locomotor activity, anxiety- and depressive-like behavior, learning and memory deficits, attention deficits, hyperalgesia, and dysphoria. These withdrawal symptoms are most pronounced within the first week after cessation of nicotine exposure. Anxiety- and depressive-like behavior, and deficits in learning and memory may persist for several months. Adolescent (4-6 weeks old) rats and mice display fewer nicotine withdrawal symptoms than adults (>8 weeks old). In adult rats and mice, females show fewer nicotine withdrawal symptoms than males. The smoking cessation drugs bupropion and varenicline reduce nicotine withdrawal symptoms in rodents. The nicotine withdrawal symptoms that are observed in rodents are similar to those observed in humans. Tobacco smoke and e-cigarette aerosol contain chemicals and added flavors that enhance the reinforcing properties of nicotine. Therefore, more valid animal models of tobacco and e-cigarette use need to be developed by using tobacco smoke and e-cigarette aerosol exposure methods to induce dependence.

Flavor additives facilitate oral self-administration of nicotine solution in mice.

Tobacco products are very addictive, partly because they contain nicotine which is reinforcing, but also because they include appealing aromas and tastes. Flavor additives are such sensory stimuli which enhance attractiveness, as well as use and abuse of tobacco and vaping products. Yet, the interaction between these flavor additives and nicotine remains poorly understood. We want to understand how flavors may reduce nicotine' aversive taste and how it may enhance its voluntary oral self-administration in mice. We first studied the effect of flavor additives on nicotine solution palatability in a free bottle choice paradigm. Second, we investigated the effect of vanilla flavoring on the different stages of nicotine (40μg/ml) oral self-administration in mice. We show that adding flavors increase nicotine palatability and facilitate acquisition and maintenance of oral self-administration when compared to nicotine-alone group. Mice adapt their operant behavior depending on changes in nicotine concentration. All mice reinstate nicotine seeking upon presentation of associated cues. Nevertheless, vanilla-flavored nicotine was not more reinforcing than vanilla-flavored water which was reinforcing enough to drive similar operant response rates. Flavor additives increase nicotine oral consumption and help maintaining operant behavior in mice. Moreover, flavors can be very attractive and can have high reinforcing value by themselves. Thus, it is crucial that the investigation on how taste signals play an important role in modulating oral nicotine intake in rodent models remains explored.

Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms

The low sensitivity (α4)3(β2)2 (LS) and high sensitivity (α4)2(β2)3 (HS) nAChR isoforms may contribute to a variety of brain functions, pathophysiological processes, and pharmacological effects associated with nicotine use. In this study, we examined the contributions of the LS and HS α4β2 nAChR isoforms in nicotine self-administration, withdrawal symptoms, antinociceptive and hypothermic effects. We utilized two nAChR positive allosteric modulators (PAMs): desformylflustrabromine (dFBr), a PAM of both the LS and HS α4β2 nAChRs, and CMPI, a PAM selective for the LS nAChR. We found that dFBr, but not CMPI, decreased intravenous nicotine self-administration in male mice in a dose-dependent manner. Unlike dFBr, which fully reverses somatic and affective symptoms of nicotine withdrawal, CMPI at doses up to 15 mg/kg in male mice only partially reduced nicotine withdrawal-induced somatic signs, anxiety-like behavior and sucrose preference, but had no effects on nicotine withdrawal-induced hyperalgesia. These results indicate that potentiation of HS α4β2 nAChRs is necessary to modulate nicotine's reinforcing properties that underlie nicotine intake and to reverse nicotine withdrawal symptoms that influence nicotine abstinence. In contrast, both dFBr and CMPI enhanced nicotine's hypothermic effect and reduced nicotine's antinociceptive effects in male mice. Therefore, these results indicate a more prevalent role of HS α4β2 nAChR isoforms in mediating various behavioral effects associated with nicotine, whereas the LS α4β2 nAChR isoform has a limited role in mediating body temperature and nociceptive responses. These findings will facilitate the development of more selective, efficacious, and safe nAChR-based therapeutics for nicotine addiction treatment.

Determination of Free Solanesol Levels in Cigarette Filters by Liquid Chromatography-Mass Spectrometry.

Solanesol, a naturally occurring constituent of tobacco, has been utilized as a good marker for environmental tobacco smoke particulate and as a noninvasive predictor of mainstream cigarette smoke tar and nicotine intake under naturalistic smoking conditions. A fast and accurate method for measuring free solanesol to assess tobacco smoke exposure is highly desirable. We have developed and validated a new environmentally friendly, high-throughput method for measuring solanesol content in discarded cigarette filter butts. The solanesol deposited in the used filters can be correlated with mainstream smoke deliveries of nicotine and total particle matter to estimate constituent delivery to smokers. A portion of filter material is removed from cigarette butts after machine smoking, spiked with internal standard solution, extracted and quantitatively analyzed using reverse-phase liquid chromatography coupled to a triple-quadrupole mass spectrometer. The new method incorporates a 48-well plate format for automated sample preparation that reduces sample preparation time and solvent use and increases sample throughput 10-fold compared to our previous method. Accuracy and precision were evaluated by spiking known amounts of solanesol on both clean and smoked cigarette butts. Recoveries exceeded 93% at both low and high spiking levels. Linear solanesol calibration curves ranged from 1.9 to 367 µg/butt with a 0.05 µg/butt limit of detection.

Rewarding Effects of Nicotine Self-administration Increase Over Time in Male and Female Rats.

Smoking and the use of other nicotine-containing products is rewarding in humans. The self-administration of nicotine is also rewarding in male rats. However, it is unknown if there are sex differences in the reward-enhancing effects of nicotine self-administration and if the rewarding effects of nicotine change over time. Rats were prepared with catheters and intracranial self-stimulation (ICSS) electrodes to investigate the effects of nicotine and saline self-administration on reward function. A decrease in thresholds in the ICSS procedure reflects an enhancement of reward function. The ICSS parameters were determined before and after the self-administration sessions from days 1 to 10, and after the self-administration sessions from days 11 to 15. During the first 10 days, there was no sex difference in nicotine intake, but during the last 5 days, the females took more nicotine than the males. During the first 10 days, nicotine self-administration did not lower the brain reward thresholds but decreased the response latencies. During the last 5 days, nicotine lowered the reward thresholds and decreased the response latencies. An analysis with the 5-day averages (days 1-5, 6-10, and 11-15) showed that the reward enhancing and stimulatory effects of nicotine increased over time. There were no sex differences in the reward-enhancing and stimulatory effects of nicotine. The nicotinic receptor antagonist mecamylamine diminished the reward-enhancing and stimulatory effects of nicotine. These findings indicate that the rewarding effects of nicotine self-administration increase over time, and there are no sex differences in the reward-enhancing effects of nicotine self-administration in rats. This study investigated the rewarding effect of nicotine and saline self-administration in male and female rats. The self-administration of nicotine, but not saline, enhanced brain reward function and had stimulatory effects. The rewarding effects of nicotine increased over time in the males and the females. Despite that the females had a higher level of nicotine intake than the males, the reward-enhancing effects of nicotine self-administration were the same. These findings suggest that in new tobacco and e-cigarette users, nicotine's rewarding effects might increase quickly, and a higher level of nicotine use in females might not translate into greater rewarding effects.

Effect Of Nicotine On The Structure Of Gastric Mucosa Of Adult Male Albino Rats And The Possible Protective Effect Of Royal Jelly (Light and Scanning Electron Microscopic study)

Background: The smoking effects on human health are well known and its impact on vital organs can leads to death in many cases There is an association between cigarette smoking and gastric lesion especially erosions .Nicotine is the main component of cigarette, and it is the cause of most of gastrointestinal hazards from erosions to cancers. Royal jelly is one of the attractive ingredients of healthy food. It has also antioxidant effect against many toxins. Its anti-inflammatory role and its role in protection from erosions and ulcers is due to its components.Aim of the work: To examine the role of royal jelly in protection against lesions on gastric mucosa caused by nicotine intake. Materials and Methods: Thirty rats were used for the study equally divided into 3groups: 1st group (10 rats) were used as a control, 2nd group (10 rats) were administrated nicotine I.P in a dose of 0.5 mg/kg body weight for 30 days , and 3rd group (10 rats) were administrated nicotine as previously +royal jelly with a dose of 300 mg/kg/ body weight every day orally for 30 days. Then they were dissected 24 hours after last dose , the stomach was prepared for examination with Haematoxylin and Eosin, Masson Trichome, Periodic Acid Schiff (PAS) stain and scanning electron microscope.Results: The rats that were injected with nicotine showed multiple histolopathological changes: erosions on the surface epithelium , degeneration of cells and distortion of the shape of the gland. Collagen fibers are more in the nicotine group, and the thickness of mucosa decreased in this group. The covering mucous layer is defective in nicotine group, rats treated with nicotine with royal jelly the stomach appeared near the control group.Conclusion: Nicotine is toxic substance to the stomach causing histopathological changes, and royal jelly prevent these hazards.

Six-month contingency management effects on smoking cessation in individuals with substance use disorders

IntroductionPersons with substance use disorders (SUD) smoke at strikingly high rates and tobacco use cessation rates are notably low in this population. Contingency Management (CM) is effective to promote substance abstinence, including tobacco, in a large range of populations. CM is scarcely implemented in clinical settings mainly due to barriers at the therapist and organizational levels.ObjectivesThe study sought to examine the additive effectiveness of CM on Cognitive-Behavioral Therapy (CBT) over long-term smoking abstinence in persons undergoing SUD treatment.MethodsA total of 54 smokers (75.9% males, Mage=46.19, SD=9.21) were randomly assigned to CBT (n=30) or to CBT+CM (n=24). Interventions consisted of eight weeks of group-based therapy. Participants were instructed to gradually reduce their nicotine intake by 20% weekly. The CM arm was voucher-based, and the primary outcome was biochemically verified tobacco abstinence (CO≤4ppm, and urine cotinine≤80ng/ml).ResultsA total of 42/54 (77.78%) participants completed the treatment (73.33% in CBT and 83.33% in CBT+CM; p=.380). At the end of treatment, participants in CBT+CM showed higher 24-hour smoking abstinence (50% vs. 20%, p=.032); however, both treatment conditions show equal abstinence rates in the remaining follow-ups (CBT1month= 13.33% vs. CBT+CM1month= 25%; CBT2months= 10% vs. CBT+CM2months= 16.66%; CBT3months= 10% vs. CBT+CM3months= 16.66%; CBT6months= 10% vs. CBT+CM6months= 8.33%; all p-values ≥ .244).ConclusionsCM facilitates early abstinence outcomes in smokers with SUD more than CBT only does. However, no additive effects of CM were observed at long-term, suggesting the convenience to intensify CM schedules or using technology platforms for incentives delivery.DisclosureNo significant relationships.

Nicotine replacement therapy: A blessing in disguise

For much of the 20th century, smoking was regarded as a socially learned habit and as a personal choice. It is only in the past decade or so that the fundamental role of nicotine in sustaining smoking behaviour has begun to be more widely accepted. It is now recognized that cigarette smoking is primarily a manifestation of nicotine addiction and that smokers have individually characteristic preferences for their level of nicotine intake. Smokers regulate the way they puff and inhale to achieve their desired nicotine dose. The link with nicotine addiction does not imply that pharmacological factors drive smoking behaviour in a simple way and to the exclusion of other influences. Social, economic, personal, and political influences all play an important part in determining patterns of smoking prevalence and cessation. Therefore, the aim of this review was to emphasize information about the nicotine replacement therapy.

Responses to Gradual and Immediate Reduction of Nicotine in Cigarettes in Young Versus Older Adult Smokers

As the FDA works to determine whether a nicotine reduction policy would benefit public health, one key question is whether to mandate an immediate or gradual reduction in nicotine levels in cigarettes. The aim of this study was to determine whether the effects of gradual versus immediate nicotine reduction on cigarettes per day (CPD), total nicotine equivalents, and subjective responses differed in younger adults versus older adults. Using data from a recent randomized trial conducted in the United States (N = 1250) that switched smokers over a 20-week period to very low nicotine content (VLNC) cigarettes either immediately, gradually (via monthly reductions in nicotine content), or not at all (control condition, normal nicotine content research cigarette), we analyzed the moderating effect of age (age 18-24 or 25+). For both age groups, CPD in the immediate condition was significantly lower relative to gradual condition (estimated mean difference of 6.3 CPD in young adults, 5.2 CPD in older adults; p's < .05). Younger and older adults in the immediate and gradual reduction conditions had lower total nicotine equivalents at Week 20 (all p's < .05) than those in the control condition; age group did not moderate this effect. Positive subjective responses to cigarettes were lower among young adults relative to older adults in the immediate condition. These results indicate that an immediate reduction in nicotine would result in beneficial effects in both young and older adults. Young adults show less positive subjective effects of smoking following switching to VLNC cigarettes relative to older adults. As researchers work to understand how a potential reduced-nicotine product standard for cigarettes may affect public health, one question is whether nicotine should be reduced immediately or gradually. This study demonstrates that both young and older adults who were switched immediately to the lowest content of nicotine smoked fewer CPD and had lower nicotine intake than those in the gradual condition. Furthermore, young adults appear to show lower positive subjective effects following switching to VLNC cigarettes relative to older adults. This is consistent with previous work demonstrating that young people appear to show lower abuse liability for VLNC cigarettes.

Adolescent nicotine and footshock exposure augments adult nicotine self-administration and drug-seeking without affecting baseline anxiety-like behaviour or stress responsivity in male rats.

Over the past decade, adolescent cigarette smoking has been declining. However, adolescent nicotine consumption via electronic cigarettes is rapidly gaining popularity. Earlier onset nicotine use is associated with increased risk of dependence. A bidirectional relationship between nicotine and stress exists; perceived stress is a predictor for nicotine use, and stress reduction is a commonly reported reason for using nicotine. We assessed the prolonged impact of adolescent high-dose nicotine and/or footshock exposure on adult nicotine self-administration, anxiety-like behaviour, and hormonal responsivity. During adolescence (postnatal day [P]28-56) male Sprague-Dawley rats were assigned to one of five groups: saline (SALPRE: 1 ml/kg, SC, every day), nicotine (NICPRE: 1 mg/kg, SC, alternating daily with saline; 14 total nicotine injections), footshock (SHOCKPRE: 8 of 0.5 s, 0.8 mA alternating sessions; saline every day), or combination nicotine and footshock (NIC+SHOCK: concurrent and alternating daily with saline, or NIC-SHOCK: alternating with saline on shock sessions). On P70, one cohort underwent spontaneous intravenous nicotine self-administration (0.03 mg/kg/infusion); another cohort was assessed for open-field behaviour (P71), then corticosterone (CORT) response to nicotine or footshock in adulthood (P72-73). Intermittent adolescent nicotine or footshock alone (NICPRE and SHOCKPRE) did not potentiate adult spontaneous nicotine intake compared to SALPRE. However, both combination groups (NIC+SHOCK, NIC-SHOCK) showed increased adult nicotine consumption without associated differences in baseline anxiety-like behaviour or CORT response. Adolescent nicotine and footshock stressors have a synergistic effect on adult nicotine consumption, enhancing nicotine intake. Avenues toward reducing stress in adolescent nicotine users may provide opportunities to reduce vulnerability to adult nicotine consumption.

Significant association of nicotine reinforcement and cue reactivity: a translational study in humans and rats.

Relapse is common amongst smokers attempting to quit and tobacco cue-induced craving is an important relapse mechanism. Preclinical studies commonly use cue-induced reinstatement of nicotine seeking to investigate relapse neurobiology. Previous research suggests dependence severity and nicotine intake history affect smoking resumption and cue-induced reinstatement of nicotine seeking. However, behavioural data may be interpreted in terms of nicotine reinforcement. This translational study investigated if individual differences in objectively assessed nicotine reinforcement strength were associated with cue-reactivity in both rats and human smokers, which to our knowledge has not been investigated before. Rats (n = 16) were trained to self-administer nicotine and were tested on a progressive ratio schedule of nicotine reinforcement, to assess reinforcer strength, and on a test of cue-induced reinstatement of nicotine seeking. Nicotine reinforcement strength was assessed in human smokers (n = 104) using a forced choice task (nicotine containing vs. denicotinised cigarettes) and self-reported cue-induced craving was assessed following exposure to smoking and neutral cues. Responding for nicotine under progressive ratio was strongly positively correlated with cue-induced reinstatement of nicotine seeking in rats. Nicotine choices in human smokers were significantly associated with cue-induced craving controlling for dependence severity, years of smoking, and urge to smoke following neutral cues. Findings suggest nicotine reinforcement strength is associated with both types of cue-induced behaviour, implying some translational commonality between cue-induced craving in human smokers and cue-induced reinstatement of nicotine seeking in rats. Findings are discussed in relation to clinical implications and whether these laboratory tasks assess drug 'wanting'.

Nicotine exacerbates atherosclerosis through a macrophage-mediated endothelial injury pathway.

Evidence suggests that nicotine intake promotes atherosclerosis. We enrolled 100 patients with coronary heart disease (CHD) and found that plaque burden, TXNIP expression, and inflammatory chemokine levels were higher in smokers than non-smokers. Additionally, patients with higher TXNIP expression in peripheral blood mononuclear cells (PBMCs) had a higher Gensini Scores and higher plasma IL-1β and IL-18 levels. Treating bone marrow-derived macrophages (BMDMs) with nicotine in vitro led to enhanced lipid phagocytosis, chemotaxis, and increased production of reactive oxygen species (ROS), which activated TXNIP/NLRP3 inflammasome signaling and promoted pyroptosis, as evidenced by caspase-1 cleavage and increased production of IL-1β, IL-18, and gasdermin D. Nicotine intake by ApoE(-/-) mice fed a high-fat diet recapitulated those phenotypes. The effects of nicotine on pyroptotic signaling were reversed by N-acetyl-cysteine, a ROS scavenger. Silencing TXNIP in vivo reversed the effects of nicotine on macrophage invasion and vascular injury. Nicotine also induced pyroptotic macrophages that contributed to the apoptotic death of endothelial cells. These findings suggest that nicotine accelerates atherosclerosis in part by promoting macrophage pyroptosis and endothelial damage. Therefore, targeting the TXNIP/NLRP3-mediated pyroptotic pathway in macrophages may ameliorate nicotine-induced endothelial damage.

Nicotine e-cigarette vapor inhalation and self-administration in a rodent model: Sex- and nicotine delivery-specific effects on metabolism and behavior.

E-cigarettes, which deliver vaporized nicotine, have dramatically risen in popularity in recent years, despite many unanswered questions about safety, efficacy in reducing dependence, and overall impact on public health. Other factors, such as sex, also play an important role in determining behavioral and neurochemical responses to drugs of abuse. In these studies, we sought to develop a protocol for vaporized e-cigarette nicotine self-administration in rats, as a foundation to better understand the differing effects of nicotine exposure routes on behavior and physiological function. We report a novel method that elicits robust nicotine vapor self-administration in male and female rats. Our findings indicate that 5-mg/ml nicotine vape solution provides a high level of consistency in lever-pressing behavior for both males and females. Moreover, in male rats, we find that such e-cigarette nicotine vapor induces similar blood levels of nicotine's main metabolite, cotinine, as that found with intravenous nicotine self-administration. Therefore, the breathing pattern during vapor exposure in males leads to similar levels of titrated nicotine intake as with intravenous nicotine self-administration. Interestingly, a differential effect was found in the females, in which the same conditions of vapor exposure led to decreased cotinine levels with vapor compared to intravenous self-administration. Finally, differences in nicotine-mediated locomotion provide further support of the physiological effects of e-cigarette vapor inhalation. Taken together, our findings reveal important sex differences in nicotine intake based on the route of exposure, and we further establish a protocol for nicotine vapor self-administration in rats.

Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers

BackgroundCompared to white smokers, Black smokers are at disproportionately higher risk for smoking-related disease, despite consuming fewer cigarettes per day (CPD). To examine racial disparities in biobehavioral influences on smoking and disease risk, we analyzed the relationship between self-reported tobacco dependence and intensity of tobacco smoke exposure per cigarette, on the one hand, and intensity of nicotine intake per cigarette, on the other. MethodsIn 270 Black and 516 white smokers, smoke exposure was measured by expired carbon monoxide (CO), and nicotine intake was measured by plasma cotinine (COT) and cotinine+3′-hydroxycotinine ([COT + 3HC]). Using linear regression analyses, we analyzed how the Fagerström Test for Cigarette Dependence (FTCD) predicted intensity of smoke exposure per cigarette (CO/CPD) and intensity of nicotine intake per cigarette (COT/CPD; [COT + 3HC]/CPD), and how race moderated these relations. ResultsOverall, Black smokers consumed fewer CPD than white smokers and had higher levels of CO/CPD, COT/CPD, and [COT + 3HC]/CPD. These elevations were most pronounced at lower levels of dependence: amongst Black smokers, FTCD negatively predicted intensity of smoke exposure as measured by CO/CPD (B = −0.12, 95% CI = −0.18, −0.05, p = 0.0003) and intensity of nicotine intake as measured by [COT + 3HC]/CPD (B = −1.31, 95% CI = −2.15, −0.46, p = 0.002). ConclusionsLow-dependence Black smokers had higher intensities of both smoke exposure and nicotine intake per cigarette compared to similarly dependent white smokers, suggesting that measures of dependence, exposure, and intake underestimate incremental risk of each cigarette to Black smokers.

Administration of N-acetylcysteine Plus Acetylsalicylic Acid Markedly Inhibits Nicotine Reinstatement Following Chronic Oral Nicotine Intake in Female Rats.

BackgroundNicotine is the major addictive component of cigarette smoke and the prime culprit of the failure to quit smoking. Common elements perpetuating the use of addictive drugs are (i) cues associated with the setting in which drug was used and (ii) relapse/reinstatement mediated by an increased glutamatergic tone (iii) associated with drug-induced neuroinflammation and oxidative stress.AimsThe present study assessed the effect of the coadministration of the antioxidant N-acetylcysteine (NAC) plus the anti-inflammatory acetylsalicylic acid (ASA) on oral nicotine reinstatement intake following a post-deprivation re-access in female rats that had chronically and voluntarily consumed a nicotine solution orally. The nicotine-induced oxidative stress and neuroinflammation in the hippocampus and its effects on the glutamate transporters GLT-1 and XCT mRNA levels in prefrontal cortex were also analyzed.ResultsThe oral coadministration of NAC (40 mg/kg/day) and ASA (15 mg/kg/day) inhibited by 85% of the oral nicotine reinstatement intake compared to control (vehicle), showing an additive effect of both drugs. Acetylsalicylic acid and N-acetylcysteine normalized hippocampal oxidative stress and blunted the hippocampal neuroinflammation observed upon oral nicotine reinstatement. Nicotine downregulated GLT-1 and xCT gene expression in the prefrontal cortex, an effect reversed by N-acetylcysteine, while acetylsalicylic acid reversed the nicotine-induced downregulation of GLT-1 gene expression. The inhibitory effect of N-acetylcysteine on chronic nicotine intake was blocked by the administration of sulfasalazine, an inhibitor of the xCT transporter.ConclusionNicotine reinstatement, following post-deprivation of chronic oral nicotine intake, downregulates the mRNA levels of GLT-1 and xCT transporters, an effect reversed by the coadministration of N-acetylcysteine and acetylsalicylic acid, leading to a marked inhibition of nicotine intake. The combination of these drugs may constitute a valuable adjunct in the treatment of nicotine-dependent behaviors.

Perceptions, symptoms, and practices of electronic cigarette users: Descriptive analysis and validation of Arabic short form vaping consequences questionnaire.

BackgroundE-cigarette (EC) use is increasing worldwide. Understanding the practices and perceptions of e-cigarette users and profiling the symptoms they experience is essential for regulating the use of such products. This study aims to investigate the practices and perceptions of e-cigarette users in Jordan and examine the symptoms (e.g. respiratory) they associate with e-cigarette use.MethodsA cross-sectional online survey was conducted to assess EC use and tobacco smoking behaviors and the corresponding health symptoms among EC users in Jordan. EC use expectancies were also assessed using the Short Form Vaping Consequences Questionnaire, which was first translated into Arabic and tested for validity and reliability.ResultsOut of the 400 EC users surveyed, 95.5% were male, 76.2% used nicotine-containing juice, and 56.8% were concurrent tobacco smokers. Further, the participants had a mean age of 28.9 years (±10.2). Among dual EC/cigarette users, 88.6% reported that they tried to quit cigarette smoking, with e-cigarette use being the most commonly tried method of smoking cessation. The smoking-related symptoms reported by regular cigarette smokers mainly included sputum production (77.5%). The participants reported that using e-cigarettes instead of tobacco cigarettes had led to improvements in their sputum production (60.8%), breathing (59%), and general wellbeing (52%). Pleasant taste, enjoyable taste sensation, and flavor were significantly stronger (P-value < 0.05) among e-cigarette users compared to dual users. Dual EC/cigarette users reported stronger perceptions in the negative consequences scale, particularly with regards to the hazardous effects of smoking on health (P-value < 0.05).ConclusionDual daily use of e-cigarettes and regular cigarettes is a common practice among EC users. We recommend that further research is conducted on dual EC/cigarette use and the potential health risks this may have (e.g. higher nicotine intake as compared to the single use of either products).

Association between Friends' Use of Nicotine and Cannabis and Intake of both Substances among Adolescents.

Nicotine and cannabis use are common among adolescents and may be associated with behavioral problems, poor academic outcomes and use disorders. The goals of this analysis were the following: (1) Describe the influence of friends’ nicotine and cannabis smoking and vaping on self-reported use. (2) Describe the relationship between friends’ nicotine and cannabis use on participants’ urinary biomarkers of nicotine (cotinine) and cannabis (11-nor-9-carboxy-Δ⁹tetrahydrocannabinol=THC-COOH). This is a secondary analysis of survey and biomarker data collected in adolescents aged 12–21 between April 2017 and April 2018, in Long Island, New York. Bivariate and multivariable analyses were conducted using SPSS 26. A cutoff value of ≥10 ng/mL was used to signify recent usage for urinary cotinine and THC-COOH levels. Over one-third of the 517 surveyed adolescents reported using tobacco and one-third reported using cannabis. A significant relationship between friends’ substance use and self-use was found. For both tobacco and cannabis, over 90% (p < 0.01) of participants with urinary biomarker levels above cutoff had friends who used the respective substance. Friends’ nicotine and friends’ cannabis use were each independently associated with urinary biomarker levels for those substances (for nicotine, beta = 88.29, p = 0.03; for cannabis, beta = 163.58, p = 0.03). Friends’ use of nicotine and cannabis is associated with adolescents’ intake, as well as the physiological exposure to those substances. These findings underscore the importance of including peer influence in the discussion with adolescents about tobacco and cannabis use.

ASSOCIATION OF SLEEP PROBLEMS AND COMMON MENTAL HEALTH PROBLEMS IN ENGINEERING STUDENTS OF SGT UNIVERSITY, GURUGRAM, INDIA

Introduction:Sleep is naturally recurring state of mind and body, characterized by altered consciousness, inhibition of nearly all voluntary muscles and reduced interactions with surroundings. Chronic disturbances can lead to poor sleep quality which may manifest as increased irritability, anxiety, tension, depression, confusion. The undergraduate years are a period of vulnerability when considering sleep problems and mental health may tend to worsen over time. Alcohol, tobacco, and stimulant beverages such as tea/ caffeine affect the quality of sleep. Students are more prone to adopt and practice maladaptive sleep hygiene such as irregular bedtime, academic pressure, internet addiction, electronic media exposure, alcohol consumption and smoking, which affects quality of sleep. Material and Methods:The study was a cross sectional, interview based, non-interventional studyconducted on the engineering students at SGT University, Budhera, Gurgaon, Haryana, India. Data was collected through questionnaires such as Pittsburgh Sleep Quality Index, The Epworth `Sleepiness Scale, Depression Anxiety Stress Scale, The general health questionnaire. Results:A total of 274 students were included in the study. The mean age was20.11 ± 1.30 years and there were more male (77.3%) students as compared to females (22.7%). Alcohol use was present in 43(11.7%) of students, cannabis intake was present in 11(4%), nicotine intake was reported by 39(14.2%) of students and only one student reported of taking opioid. DASS-A, DASS-S, DASS-D, GHQ-12, PSQI were positively correlated with each other when associations were studied individually. Conclusion:In our study,it was established that poor sleep quality in engineering students was significantly associated with poor mental and physical health.

α3* Nicotinic Acetylcholine Receptors in the Habenula-Interpeduncular Nucleus Circuit Regulate Nicotine Intake.

Allelic variation in CHRNA3, the gene encoding the α3 nicotinic acetylcholine receptor (nAChR) subunit, increases vulnerability to tobacco dependence and smoking-related diseases, but little is known about the role for α3-containing (α3*) nAChRs in regulating the addiction-related behavioral or physiological actions of nicotine. α3* nAChRs are densely expressed by medial habenula (mHb) neurons, which project almost exclusively to the interpeduncular nucleus (IPn) and are known to regulate nicotine avoidance behaviors. We found that Chrna3tm1.1Hwrt hypomorphic mice, which express constitutively low levels of α3* nAChRs, self-administer greater quantities of nicotine (0.4 mg kg-1 per infusion) than their wild-type littermates. Microinfusion of a lentivirus vector to express a short-hairpin RNA into the mHb or IPn to knock-down Chrna3 transcripts markedly increased nicotine self-administration behavior in rats (0.01-0.18 mg kg-1 per infusion). Using whole-cell recordings, we found that the α3β4* nAChR-selective antagonist α-conotoxin AuIB almost completely abolished nicotine-evoked currents in mHb neurons. By contrast, the α3β2* nAChR-selective antagonist α-conotoxin MII only partially attenuated these currents. Finally, micro-infusion of α-conotoxin AuIB (10 μm) but not α-conotoxin MII (10 μm) into the IPn in rats increased nicotine self-administration behavior. Together, these data suggest that α3β4* nAChRs regulate the stimulatory effects of nicotine on the mHb-IPn circuit and thereby regulate nicotine avoidance behaviors. These findings provide mechanistic insights into how CHRNA3 risk alleles can increase the risk of tobacco dependence and smoking-related diseases in human smokers.SIGNIFICANCE STATEMENT Allelic variation in CHRNA3, which encodes the α3 nicotinic acetylcholine receptor (nAChR) subunit gene, increases risk of tobacco dependence but underlying mechanisms are unclear. We report that Chrna3 hypomorphic mice consume greater quantities of nicotine than wild-type mice and that knock-down of Chrna3 gene transcripts in the habenula or interpeduncular nucleus (IPn) increases nicotine intake in rats. α-Conotoxin AuIB, a potent antagonist of the α3β4 nAChR subtype, reduced the stimulatory effects of nicotine on habenular neurons, and its infusion into the IPn increased nicotine intake in rats. These data suggest that α3β4 nAChRs in the habenula-IPn circuit regulate the motivational properties of nicotine.

Episodic future thinking for smoking cessation in individuals with substance use disorder: Treatment feasibility and acceptability

BackgroundSmokers with substance use disorders (SUD) smoke approximately four times more than the general population. Current efforts are focused on improving smoking cessation treatments for this population. Episodic future thinking (EFT), a novel intervention aimed at decreasing impulsive choice, has shown promising results for reducing cigarette demand in experimental settings. This feasibility study sought to examine the feasibility and preliminary EFT effects on delay discounting (DD) and nicotine intake reductions throughout treatment. MethodSmokers in substance use treatment (N = 29; 75.9% males) received an 8-week cognitive-behavioral treatment (CBT) + EFT for smoking cessation. The study assessed feasibility through successful recruitment rates, retention, and adherence to treatment. Participants' satisfaction acted as our acceptability measure. We computed nonparametric range tests to analyze changes in continuous variables. ResultsAmong interested individuals, 42 (43.75%) met the inclusion criteria, and 29 entered the treatment program. Rate of treatment completion was 65.5% (19/29). Mean (SD) sessions attended were 7(1.11), and mean patient satisfaction rating with treatment was 8.83/10. The study observed low compliance with EFT, with 15.8% (3/19) of patients practicing at least 50% of the requested times. ConclusionsCBT + EFT is acceptable for the SUD population. However, future studies should implement some adjustments to improve the adherence and feasibility of EFT, such as reducing the number of practices and temporal intervals in EFT events. Given the small sample size, and the absence of a control group, future larger scale trials are needed to elucidate EFT effects on DD and smoking cessation.