Varenicline is used to treat tobacco dependence. While varenicline decreases craving during a quit attempt, no studies have investigated its effect on cue-induced craving. Varenicline has also been shown to decrease alcohol consumption in animal and humans. This double-blind, randomized, placebo-controlled trial investigated the effect of varenicline on tobacco and alcohol cue-induced craving and alcohol consumption in dependent smokers/light drinkers. Tobacco and alcohol craving were assessed at baseline and after 2-weeks of drug administration using the QSU and ACQ. Significant decreases in cigarette and alcohol craving were observed between the pre- and post-drug session in the varenicline group on QSU Factor 1(87.5811.66 vs.70.5820.79, p=0.008) and ACQ Total (3.371.16 vs. 2.661.15, p=0.004) scores. This effect remained significant after correction for craving during neutral cues in the alcohol but not tobacco condition. No significant decreases in alcohol consumption were seen. These results suggest varenicline decreases overall craving, but not cue-induced craving specifically.

Varenicline is used to treat tobacco dependence. While varenicline decreases craving during a quit attempt, no studies have investigated its effect on cue-induced craving. Varenicline has also been shown to decrease alcohol consumption in animal and humans. This double-blind, randomized, placebo-controlled trial investigated the effect of varenicline on tobacco and alcohol cue-induced craving and alcohol consumption in dependent smokers/light drinkers. Tobacco and alcohol craving were assessed at baseline and after 2-weeks of drug administration using the QSU and ACQ. Significant decreases in cigarette and alcohol craving were observed between the pre- and post-drug session in the varenicline group on QSU Factor 1(87.5811.66 vs.70.5820.79, p=0.008) and ACQ Total (3.371.16 vs. 2.661.15, p=0.004) scores. This effect remained significant after correction for craving during neutral cues in the alcohol but not tobacco condition. No significant decreases in alcohol consumption were seen. These results suggest varenicline decreases overall craving, but not cue-induced craving specifically.

BACKGROUND: Alcohol and tobacco misuse and dependence are highly comorbid disorders. Varenicline alleviates symptoms of cigarette craving while preventing nicotine from binding to nicotinic acetylcholine receptors, thereby reducing nicotine’s reinforcing effects. Recent studies have shown that varenicline decreased alcohol self-administration in animal models and in one human study of heavy-drinking smokers. AIMS: To assess the effect of two-week varenicline (0.5-2mg) vs. placebo administration on cue-induced craving for tobacco and alcohol in smokers with heavy alcohol use (n = 24). METHODS: Subjects participated in two study visits where nicotine and alcohol craving and withdrawal were assessed with self-report questionnaires under four conditions (abstinence/one cigarette/neutral cues/tobacco-alcohol cues). RESULTS: Two-week administration of varenicline reduced tobacco-alcohol cue-induced cigarette cravings and reduced emotionality aspects of alcohol craving after smoking a cigarette compared to abstinence in heavy-drinking smokers. CONCLUSION: It is possible that varenicline may have particular advantages as a smoking cessation aid in heavy drinkers.

BACKGROUND: Alcohol and tobacco misuse and dependence are highly comorbid disorders. Varenicline alleviates symptoms of cigarette craving while preventing nicotine from binding to nicotinic acetylcholine receptors, thereby reducing nicotine’s reinforcing effects. Recent studies have shown that varenicline decreased alcohol self-administration in animal models and in one human study of heavy-drinking smokers. AIMS: To assess the effect of two-week varenicline (0.5-2mg) vs. placebo administration on cue-induced craving for tobacco and alcohol in smokers with heavy alcohol use (n = 24). METHODS: Subjects participated in two study visits where nicotine and alcohol craving and withdrawal were assessed with self-report questionnaires under four conditions (abstinence/one cigarette/neutral cues/tobacco-alcohol cues). RESULTS: Two-week administration of varenicline reduced tobacco-alcohol cue-induced cigarette cravings and reduced emotionality aspects of alcohol craving after smoking a cigarette compared to abstinence in heavy-drinking smokers. CONCLUSION: It is possible that varenicline may have particular advantages as a smoking cessation aid in heavy drinkers.

Rationale: Varenicline (VAR), a smoking cessation aid that is a partial agonist at nicotinic receptors, mimics the reinforcement-enhancing effects of nicotine. Varenicline, when accompanied by non-drug cues, is self-administered by rats, though it is unclear whether this results from varenicline acting as a primary reinforcer or a reinforcement enhancer of the cues. Objectives: This study sought to disentangle these two potential actions. Methods: Rats were allowed to self-administer intravenous nicotine, saline, or varenicline during 1-h sessions in operant chambers equipped with two levers. Five groups had concurrent access to drug infusions and a moderately reinforcing visual stimulus (VS) for responding on separate levers. Meeting the reinforcement schedule on one lever was reinforced with VAR (0.01, 0.06, 0.1 mg/kg/infusion), nicotine (0.06 mg/kg/infusion), or saline, while meeting the same schedule on the other lever delivered the VS. Additional groups were reinforced for pressing a single "active" lever and received VAR paired with the VS, the VS with response-independent infusions of VAR, or VAR alone (0.1 mg/kg/infusion). Results: Rats readily responded for VAR paired with VS on a single lever. However, when VAR was the only reinforcer contingent on a response, rats did not respond more than for saline. Conclusions: These findings show that VAR does not serve as a primary reinforcer in rats at doses that increase responding for non-drug reinforcers. These data are consistent with research showing that the primary reinforcing effects of VAR are weak, at best, and that the primary reinforcing and reinforcement-enhancing actions of nicotinic drugs are pharmacologically distinct.

Η νικοτίνη είναι ένα φυσικό συστατικό, αλκαλοειδές που συναντάται στην οικογένεια των φυτών Solanaceae και πήρε το όνομά της από το φυτό Nicotiana tabacum. Είναι ένα δηλητήριο που προσβάλει το ΚΝΣ και το ΠΝΣ. Εισέρχεται στον οργανισμό από τους πνεύμονες, κυρίως, αλλά και από το μάσημα του καπνού ή τσιχλών που την περιέχουν. Έτσι, εισέρχεται στο κυκλοφορικό σύστημα και φτάνει μέχρι τον αιματοεγκεφαλικό φραγμό, τον οποίο διαπερνά για να προχωρήσει στο ΚΝΣ (μέσα σε 10-20 δευτερόλεπτα μετά από την εισπνοή). Εκεί, ενεργοποιεί τους νικοτινικούς υποδοχείς της Ach, δρώντας ως αγωνιστής. Η νικοτίνη διεγείρει τη βιοδιαθεσιμότητα των νευροδιαβιβαστών ντοπαμίνη και σεροτονίνη, με αποτέλεσμα να επιταχύνει τη λειτουργία της καρδιάς και να αυξάνει την πίεση του αίματος. Επίσης, η νικοτίνη δρα στους εγκεφαλικούς μηχανισμούς ανταμοιβής, εμμέσως με την ενεργοποίηση των ενδογενών οπιοειδών (opioids) και άμεσα μέσω μηχανισμών της ντοπαμίνης. Οι μηχανισμοί αυτοί είναι το αίτιο εθισμού προς το κάπνισμα, αλλά και κάθε άλλου είδους εθισμού. Η διακοπή του καπνίσματος είναι μια δύσκολη διαδικασία και ενώ υπάρχουν τρόποι και θεραπείες, δεν βοηθούν όλα τα άτομα που θέλουν να διακόψουν το κάπνισμα. Τα πιο αξιοσημείωτα φάρμακα που χρησιμοποιούνται για την διακοπή του καπνίσματος είναι η βαρενικλίνη και η βουπροπιόνη. Στην παρούσα εργασία, μελετήθηκε η γενετική συσχέτιση πολυμορφισμών που πιθανώς εμπλέκονται στον εθισμό στη νικοτίνη (rs1329650), στην προδιάθεση της έναρξης (rs6265) και διακοπής (rs3025343) του καπνίσματος, αλλά και στην ανταπόκριση στη θεραπεία με βαρενικλίνη (rs2072659). Το πληθυσμιακό δείγμα, τόσο των καπνιστών (101 άτομα), όσο και της ομάδας αναφοράς - μη καπνιστών (75 άτομα) που χρησιμοποιήθηκε, προέρχεται από τον ελληνικό πληθυσμό. Οι μέθοδοι γονοτύπησης που εφαρμόσθηκαν περιλαμβάνουν τον προσδιορισμό αλληλουχίας κατά Sanger, την PCR-RFLP και την ARMS-PCR, σε συνδυασμό με ηλεκτροφόρηση σε αγαρόζη. Μια στατιστική τάση συσχέτισης (p=0,0279) ανιχνεύθηκε για τον πολυμορφισμό rs1329650 μεταξύ των καπνιστών και τον μη καπνιστών για την προδιάθεση στην εξάρτηση στη νικοτίνη. Για τους υπόλοιπους πολυμορφισμούς που μελετήθηκαν, δεν παρατηρήθηκαν στατιστικά σημαντικές συσχετίσεις με τα ερωτήματα που τέθηκαν στην παρούσα εργασία. / Nicotine is a natural ingredient (alkaloid), which is found in the plant’s family Solanaceae. Nicotine is named after the plant Nicotiana tabacum. Nicotine is a poison that affects both the CNS and PNS. It enters the body mainly through the lungs, though chewing tobacco or a nicotine-containing gum also helps on nicotine “administration”. Nicotine comes into the circulatory system, overcomes the blood brain barrier and reaches the CNS (within 10-20 seconds after inhalation), where it activates the nicotinic acetylcholine receptors (nicotine is an agonist). Nicotine stimulates the bioavailability of neurotransmitters dopamine and serotonin and therepy, it accelerates the heart rate and increases the blood pressure. Also, nicotine acts on the brain reward mechanisms, indirectly by the activation of the endogenous opioids and via the mechanisms of dopamine. These mechanisms are the cause of addiction to smoking, but also to any other type of addiction. Quitting smoking is a difficult process and while there are several ways and treatments, they do not help all the people who want to stop smoking. The most notable drugs being used for smoking cessation is varenicline and bupropion. Herein, we study the genetic correlation of polymorphisms that are possibly involved in nicotine addiction (rs1329650), the predisposition of individuals to begin (rs6265) or quit (rs3025343) smoking and response to varenicline treatment (rs2072659). The sample population studied involved two groups; smokers (101 people), and non-smokers (75 people) derived from the Greek population. The genotyping methods applied include Sanger sequencing and PCR-RFLP or ARMS-PCR followed by agarose gel electrophoresis. A statistical trend (p = 0.0279) becomes evident regarding rs1329650, when smokers and non-smokers were compared. The rest polymorphisms studied showed no statistically significant correlation.

No description available.

Smoking combustible cigarettes is the major cause of disease and death among adults living in the United States (U.S.). In fact, smoking combustible cigarettes causes nearly half a million premature deaths among U.S. adults every year.1–4 It is estimated that over 14% (equating to 34 million persons) of U.S. adults smoke cigarettes currently.2,5 This is a substantial decrease from 1965 when it was estimated that more than 42% of U.S. adults smoked cigarettes.1 This is partly attributed to the well-established evidence that smoking cigarettes causes harm to almost every human organ system5 and is associated with an elevated risk of developing cancer6, cardiovascular disease 7, pulmonary disease and respiratory illnesses.8–10 Despite the well-established health consequences of smoking cigarettes, millions of people are still smoking, which alone suggests that nicotine (the primary constituent of cigarettes) is highly addictive.3 Thankfully, smoking cessation by means of pharmacological treatments has been shown to help smokers overcome nicotine addiction. A review of the research on the efficacy of varenicline (Chantix) and Nicotine Replacement Therapy (NRT), two of the most commonly used smoking cessation treatments, reveals that both treatments increase long-term smoking abstinence rates with odds ratios of 3.85 for varenicline and 1.74 for NRT when compared to placebo.11–14 Even more, both drugs appear to be generally well-tolerated, with no known life-threatening side effects when compared to placebo. Research shows that the most common side effects for varenicline are nausea, insomnia, gastrointestinal effects, headache and abnormal dreams.11,15 The most common side effects for NRT appear to be skin irritation, insomnia, headache, nausea/vomiting and cough.11,15 Ultimately, both varenicline and NRT appear to be strong options for achieving smoking abstinence both with respect to overall efficacy and tolerability.

A vareniclina é uma substância química sintética utilizada para o tratamento de tabagismo; atua como agonista de receptores colinérgicos nicotínicos, em especial, como agonista parcial em receptores α4β2 e α3β4, e como agonista total do receptor α7. Levando em consideração que há uma tendência de ampliação do uso clínico da vareniclina para o tratamento da dependência à diversas substâncias de padrão abusivo e que há poucos estudos relacionados aos seus efeitos sobre o comportamento, cognição e sistema motor, tornam-se necessários mais estudos sobre essa substância. Assim, no presente trabalho foram estudados os efeitos da exposição prolongada (28 30 dias) de ratos à vareniclina, avaliando-se o consumo de água e de ração, o ganho de peso e o comportamento animal, por meio dos testes de campo aberto, labirinto em cruz elevado, interação social, comportamento estereotipado, labirinto de Barnes e esquiva passiva. Ainda foram feitas as avaliações dos níveis de neurotransmissores e seus metabólitos em diferentes estruturas cerebrais, bem como avaliações hematológicas, bioquímicas séricas, urinárias e estudos anatomopatológicos e histopatológicos. Foram utilizadas três doses de vareniclina: 0,03 (dose terapêutica para o ser humano), 0,1 e 0,3 mg/kg, por via oral (gavagem). Os resultados mostraram que a exposição prolongada de ratos à diferentes doses de vareniclina não provocou toxicidade, uma vez que não houve alteração no consumo médio de água e de ração e no ganho de peso avaliados semanalmente. Quanto às avaliações comportamentais, observou-se leve aumento da atividade geral no campo aberto, bem como diminuição do tempo de interação social, não sendo capaz de alterar parâmetros neuroquímicos, hematológicos, bioquímicos séricos, urinários, anatomopatológicos e histopatológicos de ratos expostos à vareniclina. / Varenicline is a synthetic chemical used for the smoking addiction treatment; it acts as an agonist of nicotinic cholinergic receptors, in particular, as a partial agonist of receptors α4β2 and α3β4 and as a full agonist of the α7 receptor. More studies about this substance are necessary, given that its clinical use is increasingly being applied to the treatment of addiction to a variety of abusive drugs. Moreover, there are few studies on vareniciline effects on behavior, cognition and the motor system. Thus, in this study the effects of prolonged (28-30 days) exposure of rats to varenicline were evaluated. It was analyzed the water and food consumption, the weight gain and the animal behavior, through open field, elevated plus maze, social interaction, stereotyped behavior, Barnes maze and passive avoidance tests. The neurotransmitter levels and their metabolites in different brain structures were measured and hematological, serum biochemistry, urinary evaluations and pathological and histological studies were carried out. We used three doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg orally (gavage). The results showed that prolonged exposure of rats to different doses of varenicline did not cause toxicity, since there were no changes in average weekly consumption of water or food nor body weight gain, which were measured weekly. As for behavioral assessments, there was a slight increase in overall activity in the open field as well as decreased time of social interaction. Varenicline was not able to change neurochemical, hematological, serum biochemical, urinary, pathology and histopathology parameters of rats.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A nicotina é considerada o principal componente psicoativo do tabaco e esta induz seus efeitos farmacológicos centrais atuando em receptores nicotínicos colinérgicos (nAChRs). A maturação dos sistemas colinérgicos é consolidada durante o período da periadolescência, o que sugere que o cérebro do adolescente é vulnerável aos efeitos de estimulantes colinérgicos. Dados os efeitos deletérios do consumo de tabaco, incluindo a dependência, têm sido desenvolvidas estratégias terapêuticas para facilitar a interrupção do uso. A mais recente é o uso da vareniclina, um agonista parcial dos nAChRs α4β2. Pouco se sabe sobre os efeitos da exposição à nicotina na adolescência e menos ainda dos efeitos de curto e longo prazos dos tratamentos disponíveis para a reversão da dependência ainda durante este período. Neste sentido, os objetivos desse trabalho foram o de estudar os comportamentos associados à ansiedade e busca por novos estímulos e a função adrenal em animais expostos à fumaça do cigarro durante a adolescência e subsequentemente tratados com procedimento para reversão de dependência à nicotina. Esse estudo utilizou 150 camundongos Suíços adolescentes (de ambos os sexos). Os animais foram expostos à solução aquosa de nicotina (50g/ml - NIC) ou de sacarina (2% - SAC) v.o. do 30o dia de vida pós-natal (PN) à PN45 e submetidos aos seguintes tratamentos por gavagem de PN45 à PN56: 1) vareniclina (0,1 ou 1,0 mg/kg/dia, VAR1 e VAR2 respectivamente); 2) veículo (VEH); 3) nicotina na dose utilizada entre PN30 e PN45 (NIC). Sete grupos experimentais foram utilizados: SACVEH, SACVAR1, SACVAR2, NICVEH, NICVAR1, NICVAR2 e NICNIC. Em PN55, os animais foram submetidos ao teste do labirinto em cruz elevado (LCE) por 5 min, e duas depois ao teste do campo vazado (CV) também por 5 min. Os tecidos coletados em PN56 (após o sacrifício dos animais) foram: adrenal esquerda para a verificação do conteúdo de catecolaminas, adrenal direita para avaliação da expressão da tirosina hidroxilase e soro para a dosagem de corticosterona. Os nossos resultados demonstraram que no final da vigência do tratamento não foram encontradas diferenças entre os grupos no comportamentos associados à ansiedade do LCE e nos associados à busca por novos estímulos no CV. Por outro lado, a análise do número de orifícios explorados no centro do CV, também utilizado como medida de ansiedade, sugerem que a vareniclina por si só e a exposição continuada à nicotina são ansiogênicas mas que que o tratamento com vareniclina após a exposição à nicotina mantém os resultados dentro da normalidade. Do ponto de vista endócrino, o conteúdo adrenal de catecolaminas foi corrigido pelo tratamento com vareniclina, os níveis séricos de corticosterona foram aumentados pela exposição à nicotina enquanto o tratamento com vareniclina aumentou a expressão de tirosina hidroxilase. Nosso estudo indica que, no final da vigência do tratamento, tanto aspectos comportamentais como endócrinos estão significativamente afetados em nosso modelo de exposição à nicotina durante a adolescência e tratamento subsequente com vareniclina. Estudos futuros deverão avaliar estes parâmetros em períodos posteriores, com o objetivo de verificar se as alterações observadas persistem na vida adulta. / Nicotine is considered the main psicoactive component of tobacco and it induce its central pharmacological effects by acting on cholinergic nicotinic receptors (nAChRs). The maturation of the cholinergic system is consolidated during the periadolescent period, which suggests that the adolescent brain is vulnerable to the effects of cholinergic stimulants. Considering the deleterious effects of tobacco consumption, including addiction, several therapeutic strategies are being developed to aid in the interruption of consumption. Varenicline treatment, a partial agonist of the α4β2 nAChRs is one of the most recent ones. Little is known regarding the effects of nicotine exposure during adolescence and even less is known regarding the short and long term effects of the available treatments for addiction during this period. In this sense, the aim of the present work is to study the behaviors associated with anxiety and novelty seeking, as well as adrenal function, in animals exposed to nicotine during adolescence and subsequently treated with a procedure to cure addiction to nicotine. This study used 150 adolescent Swiss mice of both sexes. The animals were exposed (orally) to a nicotine (50g/ml - NIC) solution or to a saccharine (2% - SAC) solution from the 30th postnatal day (PN) to PN45 and then treated by gavage with one of the following substances from PN45 to PN56: 1) vareniclina (0.1 or 1.0 mg/kg/day - VAR1 and VAR2 respectively); 2) vehicle (VEH); 3) nicotine (using the dose previously used from PN30 to PN45 - NIC). Seven experimental groups were used: SACVEH, SACVAR1, SACVAR2, NICVEH, NICVAR1, NICVAR2 and NICNIC. On PN55, the animals were tested in the elevated plus maze (EPM) for 5 min and, 2 h later, they were tested for 5 min on the hole board arena (HB). The tissue samples collected on PN56 (after the animals sacrifice) were: left adrenal gland for the analysis of catecholamine content; right adrenal gland for the analysis of tyrosine hidroxilase expression; serum for the analysis of corticosterone concentration. Our results show that by the end of the treatment no differences were observed between groups regarding behaviors associated with anxiety in the EPM and those associated with novelty-seeking in the HB. Conversely, the analysis of the number of explored holes on the center of the HB, also used as a measure of anxiety, suggest that varenicline by itself and the continued exposure to nicotine are anxiogenic but that varenicline treatment following nicotine exposure keeps results within normal levels. Regarding the endocrine system, the catecholamine adrenal content was corrected by varenicline treatment, the serum corticosterone levels were increased by nicotine exposure and the tyrosine hidroxilase expression was increased by varenicline treatment. Our study indicates that, by the end of the treatment, behavioral as well as endocrine parameters were affected in our model of nicotine exposure during adolescence and subsequent varenicline treatment. Further studies will have to address this parameters in later periods with then aim of verifying whether the observed alterations persist up to adulthood.