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BACKGROUND: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD. METHODS: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples. RESULTS: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose. CONCLUSION: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT04433767).
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Afeto , Antidepressivos , Função Executiva , Nicotina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Cutânea , Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Quimioterapia Combinada , Função Executiva/efeitos dos fármacos , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Nicotina/uso terapêutico , Dispositivos para o Abandono do Uso de Tabaco , Resultado do TratamentoRESUMO
BACKGROUND: Switching to Very Low Nicotine Content (VLNC) cigarettes reduces toxicant exposure and nicotine dependence, and may improve smoking cessation. However, non-compliance with VLNCs is often high, which may reduce their effectiveness. Here, we conducted secondary analyses of a pilot smoking cessation trial utilizing VLNCs to examine associations between pre-cessation VLNC compliance and changes in smoking rate, dependence, and abstinence self-efficacy, as well as quit outcomes. METHODS: People who smoke daily (n=35) engaged in a 4-week pre-cessation intervention including VLNCs, transdermal nicotine patch, and behavioral counseling. After quit date, participants received 8 weeks of nicotine replacement therapy and 4 additional behavioral sessions, and were followed for 10 weeks to assess abstinence. Compliance with VLNCs was assessed biweekly during pre-cessation using timeline follow-back. Statistical analyses examined associations between VLNC compliance and a) changes in smoking rate, dependence and abstinence self-efficacy over the course of study cigarette use; and b) time to relapse, controlling for other smoking variables. RESULTS: Greater compliance during the second half of study cigarette use was associated with subsequent improvement in self-efficacy (p<.05). Increased self-efficacy and VLNC compliance both predicted lower likelihood of relapse. Nicotine dependence and cigarettes per day both decreased following study cigarette use, but were unrelated to compliance or relapse. CONCLUSIONS: Compliance with VLNCs prior to quitting increased abstinence self-efficacy and predicted better quit outcomes above and beyond baseline smoking characteristics. Although preliminary, these findings suggest that identifying strategies to promote exclusive use of VLNCs during a brief pre-cessation window may be beneficial.
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Nicotina , Autoeficácia , Abandono do Hábito de Fumar , Tabagismo , Humanos , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Nicotina/uso terapêutico , Projetos Piloto , Tabagismo/terapia , Tabagismo/psicologia , Dispositivos para o Abandono do Uso de Tabaco , Cooperação do Paciente , Resultado do Tratamento , Produtos do TabacoRESUMO
Importance: Most people who smoke do not quit on their initial attempt. Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT). Design, Setting, and Participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic. Interventions: The initial treatment was 2 mg/d of varenicline or the combined replacement therapy of a 21-mg patch plus 2-mg lozenge. The rerandomized participants either continued with their initial therapies, switched between varenicline and CNRT, or increased dosages either to 3-mg or more of varenicline or to a 42-mg patch and lozenges. All received weekly brief counseling. Main Outcomes and Measures: Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks. Results: The 490 randomized participants (210 female [43%], 287 non-Hispanic White [58%], mean age, 48.1 years) smoked an average of 20 cigarettes per day. After the first phase, 54 participants in the CNRT group were abstinent and continued their therapy; of the 191 who were not abstinent, 151 were rerandomized, and the 40 who did not return for rerandomization were assigned to continue their initial CNRT condition in phase 2. The end-of-treatment abstinence rate for the 191 phase 1 nonabstainers was 8% (95% credible interval [CrI], 6% to 10%) for the 90 (47%) who continued at the dosage condition, 14% (CrI, 10% to 18%) for the 50 (33%) who increased their dosage, and 14% (95% CrI, 10% to 18%) for the 51 (34%) who switched to varenicline (absolute risk difference [RD], 6%; 95% CrI, 6% to 11%) with more than 99% posterior probability that either strategy conferred benefit over continuing the initial dosage. After the first phase, 88 participants in the varenicline group were abstinent and continued their therapy; of the 157 who were not abstinent, 122 were rerandomized and 35 who did not return for rerandomization were assigned to continue with the varenicline condition. The end-of-treatment abstinence rate for the 157 phase 1 nonabstainers was 20% (95% CrI, 16% to 26%) for the 39 (32%) who increased their varenicline dosage, 0 (95% CrI, 0 to 0) for the 41 (34%) who switched CNRT, and 3% (95% CrI, 1% to 4%) for the 77 (49%) who were assigned to the continued varenicline condition (absolute RD, -3%; 95% CrI, -4% to -1%) with more than 99% posterior probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage. Furthermore, increasing the varenicline dosage had an absolute RD of 18% (95% CrI, 13% to 24%) and a more than 99% posterior probability of conferring benefit. The secondary outcome of continuous abstinence at 6 months indicated that only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages. Conclusions and Relevance: For individuals who smoked but did not achieve abstinence after treatment with varenicline, increasing the dosage enhanced abstinence vs continuing, whereas for nonabstainers initially treated with CNRT, a dosage increase or switch to varenicline enhanced abstinence and may be viable rescue strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT02271919.
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Nicotina , Agonistas Nicotínicos , Agentes de Cessação do Hábito de Fumar , Abandono do Hábito de Fumar , Vareniclina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Nicotina/uso terapêutico , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/uso terapêutico , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Falha de Tratamento , Vareniclina/uso terapêutico , Vareniclina/administração & dosagem , Vareniclina/efeitos adversos , BrancosRESUMO
Tobacco smoking is widespread in Germany. An increase in the number of teenagers and young adults that smoke has recently been a cause for concern. The high prevalence in Germany is contrasted by inadequate preventive measures compared to international standards. Smoking behavior should always be inquired about and documented in the same way as vital signs. All smokers, regardless of the reason for contact and motivation, should receive short, low-threshold advice, e.g. using the ABC approach (ask, brief advice, cessation). In addition to repeated advice and referral to further services, the use of nicotine replacement or drug therapy is essential for the success of quitting. The combination of long- and short-acting nicotine replacement products doubles the success rate. Electronic nicotine delivery systems are not recommended for smoking cessation.
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Abandono do Hábito de Fumar , Abandono do Uso de Tabaco , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Dispositivos para o Abandono do Uso de TabacoRESUMO
Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3ß4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.
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Receptores Nicotínicos , Tabagismo , Humanos , Nicotina/uso terapêutico , Tabagismo/tratamento farmacológico , Recompensa , Hormônio Liberador da Corticotropina/farmacologia , RecidivaRESUMO
BACKGROUND: Few studies have examined the effect of baseline attitudes toward nicotine replacement therapy (NRT) on its actual adherence in a smoking cessation intervention. PURPOSE: This study (i) examined the predictability of baseline variables (quantitative data) on NRT adherence and (ii) explored the congruence of participants' statements about NRT products (qualitative data) during counseling sessions with their baseline attitudes. METHODS: This is a mixed-methods research study using a convergent parallel design. Participants included 74 individuals in the treatment group who received behavioral counseling and combination NRT. A Poisson regression analysis was performed to identify baseline variables predicting NRT adherence. Thematic analysis was completed with a subset of participants (n = 38) who varied in NRT attitude scores and adherence. A joint display was created to integrate quantitative and qualitative data and discover convergence. RESULTS: Approximately 59% of the participants (41/74) used NRT continuously for ≥5 weeks. Having negative attitudes toward NRT and depressive symptoms predicted NRT adherence even after controlling for education and anxiety symptoms. Thematic analysis revealed that NRT adherence is a learning process that consists of the following three distinctive but interrelated phases: (i) information needs, (ii) comprehensive readiness, and (iii) experiential learning. Of the 38 participants, 34 (89.5%) showed convergence between baseline attitude scores and statements about NRT made during counseling sessions. CONCLUSIONS: Individuals who have negative attitudes toward NRT are less likely to use the products in a smoking cessation intervention. Counselors should assess attitudes toward NRT at baseline and address them proactively during counseling sessions.
Few research studies have explored how attitudes toward nicotine substitutes (nicotine patches, gum, and lozenges) affect people's adherence to those substitutes (using them consistently as directed). This study examined (i) whether age, gender, education, attitudes toward the substitutes, and depressive and anxiety symptoms would predict peoples' adherence to these nicotine substitutes during a study to help stop smoking and (ii) whether peoples' statements about their experiences with the substitutes would reveal any patterns. The study was conducted with 74 individuals who received behavioral counseling and combination nicotine substitutes. Having negative attitudes toward the substitutes and depressive symptoms predicted adherence. Age, gender, education, positive attitudes, and anxiety symptoms did not. Statements from a subset of participants (n = 38) revealed that adherence to the substitutes is a learning process that consists of the following three phases: (i) needing more information assuring the safety of the substitutes, (ii) being mentally and situationally ready, and (iii) learning while being involved in the process such as "trial and error." Individuals who have negative attitudes toward the substitutes are less likely to use them, and counselors should assess attitudes toward nicotine replacement therapy before suggesting their use and address these attitudes proactively during smoking cessation counseling sessions.
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Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/psicologia , Nicotina/uso terapêutico , Terapia de Substituição da Nicotina , Dispositivos para o Abandono do Uso de Tabaco , Aconselhamento/métodosRESUMO
BACKGROUND: Systemic inflammation in which lipopolysaccharide (LPS) is released into circulation can cause cognitive dysfunction and we have previously shown that LPS impaired working memory (WM) which refers to the ability to guide incoming behavior by retrieving recently acquired information. However, the mechanism is not very clear, and currently, there is no approved strategy to improve inflammation-induced WM deficit. Notably, epidemiological studies have demonstrated a lower occurrence rate of inflammatory-related diseases in smoking patients, suggesting that inflammation-induced WM impairment may be improved by nicotine treatment. Here, our object is to investigate the effect and potential mechanisms of acute and chronic nicotine treatment on LPS-produced WM deficiency. METHODS: Delayed alternation T-maze task (DAT) was applied for evaluating WM which includes both the short-term information storage and the ability to correct errors in adult male mice. Immunofluorescence staining and immunoblotting were used for assessing the levels and distribution of CREB-regulated transcription coactivator 1 (CRTC1) and hyperpolarization-activated cation channels 2 (HCN2) in the medial prefrontal cortex (mPFC) and hippocampus. Quantitative PCR and ELISA were employed for analyzing the mRNA and protein levels of TNF-α and IL-1ß. RESULTS: Our results revealed that administration of LPS (i.p.) at a dose of 0.5 mg/kg significantly produced WM impairment in the DAT task accompanied by an increase in IL-1ß and TNF-α expression in the mPFC. Moreover, intra-mPFC infusion of IL-1Ra, an IL-1 antagonist, markedly alleviated LPS-induced WM deficiency. More important, chronic (2 weeks) but not acute nicotine (0.2 mg/kg, subcutaneous) treatment significantly alleviated LPS-induced WM deficiency by upregulating CRTC1 and HCN2. Of note, intra-mPFC infusion of HCN blocker ZD7288 produced significant WM deficiency. CONCLUSIONS: In summary, in this study, we show that chronic nicotine treatment ameliorates acute inflammation-induced working memory deficiency by increasing CRTC1 and HCN2 in adult male mice.
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Memória de Curto Prazo , Nicotina , Humanos , Camundongos , Masculino , Animais , Memória de Curto Prazo/fisiologia , Nicotina/farmacologia , Nicotina/uso terapêutico , Nicotina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/toxicidade , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Hipocampo/metabolismo , Fatores de Transcrição/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Canais de Potássio/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismoRESUMO
BACKGROUND AND AIMS: Smoking is considered the main cause of preventable death world-wide. This study aimed to review the efficacy and safety of cytisine for smoking cessation. METHODS: This review included an exhaustive search of databases to identify randomized controlled trials (RCTs) in health centers of any level with smokers of any age or gender investigating the effects of cytisine at standard dosage versus placebo, varenicline or nicotine replacement therapy (NRT). RESULTS: We identified 12 RCTs. Eight RCTs compared cytisine with placebo at the standard dose covering 5922 patients, 2996 of whom took cytisine, delivering a risk ratio (RR) of 2.25 [95% confidence interval (CI) = 1.42-3.56; I2 = 88%; moderate-quality evidence]. The greater intensity of behavioral therapy was associated directly with the efficacy findings (moderate-quality evidence). The confirmed efficacy of cytisine was not evidenced in trials conducted in low- and middle-income countries. We estimate a number needed to treat (NNT) of 11. Two trials compared the efficacy of cytisine versus NRT, and the combination of both studies yields modest results in favor of cytisine. Three trials compared cytisine with varenicline, without a clear benefit for cytisine. Meta-analyses of all non-serious adverse events in the cytisine group versus placebo groups yielded a RR of 1.24 (95% CI = 1.11-1.39; participants = 5895; studies = 8; I2 = 0%; high-quality evidence). CONCLUSIONS: Cytisine increases the chances of successful smoking cessation by more than twofold compared with placebo and has a benign safety profile, with no evidence of serious safety concerns. Limited evidence suggests that cytisine may be more effective than nicotine replacement therapy, with modest cessation rates.
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Alcaloides , Alcaloides Quinolizidínicos , Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/métodos , Vareniclina/uso terapêutico , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Bupropiona/uso terapêutico , Benzazepinas/efeitos adversos , Quinoxalinas/efeitos adversos , Alcaloides/uso terapêutico , Azocinas/uso terapêutico , Quinolizinas/uso terapêuticoRESUMO
OBJECTIVE: We offer an overview of ADHD research using mouse models of nicotine exposure. METHOD: Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. RESULTS: Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. CONCLUSION: Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Gravidez , Camundongos , Animais , Feminino , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Nicotina/uso terapêutico , Neurobiologia , Camundongos Endogâmicos C57BL , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Descoberta de Drogas , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêuticoRESUMO
INTRODUCTION: Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication. AIMS AND METHODS: The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6-week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 andâ ≥â 0.31, respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication and phenotype concordance, and estimates of relative risk (RR) of quitting. RESULTS: We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication and phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RRâ =â 2.93 [1.42, 6.03] and RRâ =â 2.52 [1.12, 5.64], respectively) compared to nicotine replacement therapy. Non-optimal medication and phenotype concordance decreased likelihood of quit success (RRâ =â 0.44 [0.22, 0.91]) compared to optimal concordance. CONCLUSIONS: This exploratory study found associations between quit success and tobacco cessation medication as well as medication and phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people. IMPLICATIONS: These results broadly support additional community-engaged research to improve medication and phenotype concordance in tribal health settings. Such future research on implementing meditcation and phenotype concordance holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking.
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Abandono do Hábito de Fumar , Fatores Sociodemográficos , Adulto , Humanos , Indígena Americano ou Nativo do Alasca/genética , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Estudos Retrospectivos , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de TabacoRESUMO
Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q has been shown to be useful in the treatment of non-small cell lung cancer (NSCLC), as demonstrated by in vitro/in vivo studies, due to its antitumor, anti-inflammatory, anti-proliferative, anti-angiogenesis, and apoptotic properties. Some flavonoids (flavone, anthocyanins, and proanthocyanidins) have been demonstrated to be effective in nicotine-induced NSCLC treatment. However, the molecular mechanisms of quercetin derivatives (QDs) in nicotine-induced NSCLC treatment remain unclear. Thus, this review aims to summarize the available literature on the therapeutic effects of QDs in nicotine-induced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nicotina/farmacologia , Nicotina/uso terapêutico , Antocianinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Flavonoides/farmacologiaRESUMO
Despite decades of research and anti-tobacco messaging, nicotine addiction remains an important public health problem leading to hundreds of thousands of deaths each year. While fundamental studies have identified molecular, circuit-level and behavioral mechanisms important for nicotine reinforcement and withdrawal, recent studies have identified additional pathways that are important for both nicotine seeking and aversion. In particular, although dopaminergic mechanisms are necessary for nicotine-dependent reward and drug-seeking, novel glutamate and GABA signaling mechanisms in the mesolimbic system have been identified for their contributions to reward-related behaviors. An additional area of active investigation for nicotine addiction focuses on molecular mechanisms in the habenula-interpeduncular pathway driving nicotine aversion and withdrawal. Across all these domains, sex differences in the molecular basis of nicotine-induced behaviors have emerged that identify important new directions for future research. Recent studies reviewed here highlight additional pathways that could provide therapeutic targets for smoking cessation and problematic nicotine vaping.
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Receptores Nicotínicos , Tabagismo , Feminino , Humanos , Masculino , Nicotina/farmacologia , Nicotina/uso terapêutico , Tabagismo/tratamento farmacológico , Dopamina/metabolismo , Agonistas Nicotínicos/farmacologia , Agonistas Nicotínicos/uso terapêutico , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/uso terapêuticoRESUMO
Importance: Adaptive pharmacotherapy, ie, starting a medication regimen and then modifying that regimen based on patient response, is common in many medical domains but is not common in smoking cessation. Recently, studies have found that adaptive treatment using precessation nicotine patches is efficacious for smoking cessation; however, adaptive treatment using precessation varenicline and adaptive treatment in clinical practice settings have not been fully assessed. Objective: To determine whether adaptive pharmacotherapy leads to higher smoking abstinence rates than standard pharmacotherapy in a clinical practice setting. Design, Setting, and Participants: This double-blinded stratified placebo-controlled randomized clinical trial compared adaptive treatment with standard treatment for smoking cessation. The study was conducted at a university health system in Durham, North Carolina, from February 2018 to May 2020 and was stopped early due to COVID-19. Data were analyzed as intent-to-treat from May 24, 2021, to February 27, 2022. Interventions: Participants were allowed to choose varenicline or nicotine patches and were then randomized to adaptive or nonadaptive (standard) treatment. Participants started on their chosen medication (adaptive) or placebo (standard) 4 weeks before their target quit day. Two weeks later, participants were assessed for treatment response. Adaptive participants who did not decrease daily cigarettes smoked by at least 50% (nonresponders) received bupropion in addition to their chosen medication. Participants in the adaptative treatment group who did decrease daily cigarettes smoked by at least 50% (responders) and participants in the standard treatment group received additional placebo bupropion. Participants in the standard treatment group received varenicline starting 1 week before the target quit date or nicotine patches starting on the target quit day. All participants received brief behavioral support. Main Outcome and Measures: The main outcome was biochemically verified 30-day continuous smoking abstinence 12 weeks after their target quit smoking day. Other measures included demographic characteristics, smoking history, and repeated smoking assessments. Results: Of the planned 300 participants, a total of 188 participants (mean [SD] age, 49.1 [12.5] years; 102 [54%] female) were enrolled before the trial was stopped because of the COVID-19 pandemic. A total of 127 participants chose to use varenicline, including 64 randomized to adaptive treatment and 63 randomized to standard treatment, and 61 participants chose to use nicotine patches, including 31 randomized to adaptive treatment and 30 randomized to standard treatment. At baseline, participants smoked a mean (SD) of 15.4 (7.3) cigarettes per day. At 12 weeks after the target quit day, biochemically verified 30-day continuous smoking abstinence was observed in 23 of 95 participants (24%) in the adaptive treatment group and 8 of 93 participants (9%) in the standard treatment (odds ratio [OR], 3.38; 95% CI, 1.43-7.99; P = .004); among participants who used varenicline, 30-day continuous abstinence was 18 participants (28%) in the adaptive treatment group, and 5 participants (8%) in the standard treatment group (OR, 4.54; 95% CI, 1.57-13.15); among participants who used nicotine patches, 30-day continuous abstinence was 5 participants (16%) in the adaptive treatment group and 3 participants (10%) in the standard treatment group (OR, 1.73; 95% CI, 0.38-7.99). Sleep problems were more common for participants in the varenicline adaptive treatment group than in the varenicline standard treatment group (rate ratio, 1.74; 95% CI, 1.18-2.58; P = .03). Conclusions and Relevance: This randomized clinical trial found that adaptive pharmacotherapy was efficacious for smoking cessation treatment in a practice setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02501265.
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COVID-19 , Abandono do Hábito de Fumar , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Vareniclina/uso terapêutico , Bupropiona , Nicotina/uso terapêutico , Pandemias , Dispositivos para o Abandono do Uso de TabacoRESUMO
INTRODUCTION: Unlike other U.S. geographical regions, cigarette smoking prevalence remains stagnant in rural Appalachia. One avenue for reaching rural residents with evidence-based smoking cessation treatments could be utilizing community pharmacists. This paper describes the design, rationale, and analysis plan for a mixed-method study that will determine combinations of cessation treatment components that can be integrated within community pharmacies in rural Appalachia. The aim is to quantify the individual and synergistic effects of five highly disseminable and sustainable cessation components in a factorial experiment. METHODS: This sequential, mixed-method research design, based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, will use a randomized controlled trial with a 25 fully crossed factorial design (32 treatment combinations) to test, alone and in combination, the most effective evidence-based cessation components: (1) QuitAid (yes vs. no) (2) tobacco quit line (yes vs. no) (3) SmokefreeTXT (yes vs. no) (4) combination NRT lozenge + NRT patch (vs. NRT patch alone), and (5) eight weeks of NRT (vs. standard four weeks). RESULTS: Logistic regression will model abstinence at six-months, including indicators for the five treatment factors and all two-way interactions between the treatment factors. Demographic and smoking history variables will be considered to assess potential effect modification. Poisson regression will model quit attempts and percent of adherence to treatment components as secondary outcomes. CONCLUSION: This study will provide foundational evidence on how community pharmacies in medically underserved, rural regions can be leveraged to increase utilization of existing evidence-based tobacco cessation resources for treating tobacco dependence. CLINICAL TRIALS: NCT05660525.
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Fumar Cigarros , Farmácia , Abandono do Hábito de Fumar , Humanos , Adulto , Nicotina/uso terapêutico , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de TabacoRESUMO
INTRODUCTION: Our previous study showed major changes in biomarkers on quitting compared to the smoking state. They reflected a decrease in inflammation, endothelial activation, and oxidative stress, as well as an improved lipid profile. Nicotine replacement therapy (NRT) is effective to increase the rate of successful quitting, but healthcare professionals may have concerns to prescribe this first-line smoking cessation treatment because its effect on inflammation and related processes is controversial. AIMS AND METHODS: The present study assessed the influence of NRT on biomarkers of inflammation, endothelial function, oxidative stress, and lipids, in people who quit smoking. Sixty-five subjects who daily smoke cigarettes were recruited and followed on quitting. Thirty-five quit using NRT and thirty quit without NRT. Biomarkers of inflammation, endothelial function, oxidative stress, and lipids were quantified at baseline when actively smoking and after cessation in the presence of NRT or not. RESULTS: Changes in biomarkers on quitting did not differ according to the treatment used. No difference was found when comparing participants who were exposed to NRT and those who were not. CONCLUSIONS: These results may indicate that NRT has no effect on inflammation, endothelial function, oxidative stress, and lipids, when used as a medication aid for quitting smoking. IMPLICATIONS: This study provides new evidence to support the safety profile of NRT products regarding the biomarkers of endothelial function, oxidative stress, inflammation, and lipids.
Assuntos
Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/métodos , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Fumantes , Dispositivos para o Abandono do Uso de Tabaco , Biomarcadores , Inflamação , Estresse Oxidativo , LipídeosRESUMO
INTRODUCTION: Tobacco smoking rates in high-income countries are greater in rural, regional, and remote (RRR) areas compared to cities. Yet, there is limited knowledge about interventions targeted to RRR smokers. This review describes the effectiveness of smoking cessation interventions for RRR smokers in supporting smoking abstinence. AIMS AND METHODS: Seven academic databases were searched (inception-June 2022) for smoking cessation intervention studies to include if they reported on RRR residents of Australia, Canada, or the United States, and short- (<6 months) or long-term (≥6 months) smoking abstinence outcomes. Two researchers assessed study quality, and narratively summarized findings. RESULTS: Included studies (n = 26) were primarily randomized control (12) or pre-post (7) designs, from the United States (16) or Australia (8). Five systems change interventions were included. Interventions included cessation education or brief advice, and few included nicotine monotherapies, cessation counseling, motivational interviewing, or cognitive behavioral therapy. Interventions had limited short-term effects on RRR smoking abstinence, decreasing markedly beyond 6 months. Short-term abstinence was best supported by contingency, incentive, and online cessation interventions, and long-term abstinence by pharmacotherapy. CONCLUSIONS: Cessation interventions for RRR smokers should include pharmacotherapy and psychological cessation counseling to establish short-term abstinence, and identify effective means of maintaining abstinence beyond 6 months. Contingency designs are a suitable vehicle for psychological and pharmacotherapy support for RRR people who smoke, and intervention tailoring should be explicitly considered. IMPLICATIONS: Smoking disproportionately harms RRR residents, who can encounter access barriers to smoking cessation support. High-quality intervention evidence and outcome standardization are still required to support long-term RRR smoking abstinence.
Assuntos
Terapia Cognitivo-Comportamental , Abandono do Hábito de Fumar , Humanos , Países Desenvolvidos , Nicotina/uso terapêutico , Terapia ComportamentalRESUMO
BACKGROUND: Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on nicotine interactions with illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to modulate use liability of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high nicotine-prescription psychostimulant co-use. METHODS: We searched databases for literature investigating acute and chronic nicotine and prescription psychostimulant interactions. Inclusion criteria were that participants/subjects had to experience nicotine and a prescription psychostimulant compound at least once in the study, in addition to assessment of their interaction. RESULTS AND CONCLUSIONS: Nicotine clearly interacts with d-amphetamine and methylphenidate in a variety of behavioral tasks and neurochemical assays assessing co-use liability across preclinical, clinical, and epidemiological research. The currently available research suggests research gaps examining these interactions in women/female rodents, in consideration of ADHD symptoms, and how prescription psychostimulant exposure influences later nicotine-related outcomes. Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Feminino , Humanos , Nicotina/farmacologia , Nicotina/uso terapêutico , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Dextroanfetamina/uso terapêutico , PrescriçõesRESUMO
Aims and Objectives: Tobacco dependence is widely prevalent and a harmful chronic disorder. Achieving long-term tobacco abstinence is an important public health goal. This study aims to assess the long-term effectiveness of moderate-intensity treatment for tobacco cessation in the dental clinic setting. Materials and Methods: Out of 1206 subjects registered to the Tobacco cessation clinic (TCC) during this time period, only 999 of them completed the 1-year follow-up period. The mean age was 45.9 ± 9 years. Six hundred and three (60.3%) of these subjects were male and 396 (39.6%) of them were females. Five hundred and fifty-eight (55.8%) used smoking tobacco and 441 (44.1%) used smokeless tobacco. Patients received tailored behavioral counseling, educational material, and pharmacotherapy consisting of nicotine replacement therapy (NRT) and\or NON-NRT. Patients were monitored by phone or clinic visits for 11 months. Results: Outcomes assessed were complete abstinence, harm reduction (>50% reduction), no change and lost to follow-up. At the end of 12 months the tobacco quit rate was180 (18%), tobacco reduction >50% was 342 (34.2%), no change 415 (41.5%) and relapse 62 (6.2%). Conclusions: Our study has identified adequate quit-rates in a cohort of dental patients attending a hospital-based TCC.
Assuntos
Abandono do Hábito de Fumar , Abandono do Uso de Tabaco , Feminino , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Nicotina/uso terapêutico , Seguimentos , Dispositivos para o Abandono do Uso de Tabaco , Doença CrônicaRESUMO
Smoking and second-hand smoke strongly increase incidence of diabetes and probability for its complications. Smoking cessation can lead to weight gain and increased diabetes risk; however, it decreases cardiovascular and total mortality. A basal diagnostics (Fagerström Test, exhaled CO) is the basis for successful smoking cessation. Supporting medication include Varenicline, Nicotine Replacement Therapy and Bupropion. Socio-economic as well as psychological factors play an important role for smoking and smoking cessation. Heated tobacco products (like the Ecigarette) are no healthy alternative to cigarettes and are associated with increased morbidity and mortality.Moderate consumption of alcohol possibly decreases risk for diabetes and cardiovascular diseases. Selection bias and underreporting in studies maybe contribute to a too optimistic view. On the other hand, alcohol increases in a dose dependant fashion excess morbidity and disability adjusted life years, especially by cancer, liver diseases and infections.
Assuntos
Diabetes Mellitus , Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Produtos do Tabaco , Humanos , Agonistas Nicotínicos/uso terapêutico , Nicotina/uso terapêutico , Benzazepinas/uso terapêutico , Dispositivos para o Abandono do Uso de Tabaco , Bupropiona/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Etanol , FumarRESUMO
BACKGROUND: L-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid detected in green tea leaves, is used as a dietary supplement to attenuate stress and enhance mood and cognition. Furthermore, L-theanine induces anxiolytic effects in humans. Recently, L-theanine was reported to reduce morphine physical dependence in primates, suggesting the potential usefulness of L-theanine for drug dependence intervention. OBJECTIVE: The aim of this study is to determine whether L-theanine attenuates nicotine-withdrawal (somatic and affective signs) and nicotine reward in mice. We also investigated the effects of L-theanine on nicotinic receptors binding and function. METHODS: ICR male mice rendered dependent to nicotine through implanted subcutaneous osmotic minipumps for 14 days undertook precipitated nicotine withdrawal by mecamylamine on day 15. Anxiety-like behaviors using LDB, somatic signs observation and hot plate latency were assessed consecutively after treatment with L-theanine. Furthermore, we examined the effect of L-theanine on acute nicotine responses and nicotine conditioned reward in mice and on expressed nicotinic receptors in oocytes. KEY FINDINGS: L-theanine reduced in a dose-dependent manner anxiety-like behavior, hyperalgesia and somatic signs during nicotine withdrawal. Also, L-theanine decreased the nicotine CPP, but it did not affect the acute responses of nicotine. Finally, L-theanine did not alter the binding or the function of expressed α4ß2 and α7 nAChRs. CONCLUSION: Our results support the potential of L-theanine as a promising candidate for treating nicotine dependence.