Treatment Of Nicotine Dependence Research Articles

Harms of Electronic Cigarettes: What the Healthcare Provider Needs to Know.

Electronic cigarettes (e-cigarettes) reached the market without either extensive preclinical toxicology testing or long-term safety trials that would be required of conventional therapeutics or medical devices. E-cigarettes are considered a tobacco product and as such have no manufacturing quality or safety standards. A growing body of evidence documents severe harms from e-cigarette use, including injuries from product explosions, nicotine poisoning, and severe lung diseases. Commonly used e-cigarette components have significant inhalation toxicity. Emerging evidence from laboratory studies suggests substantial reason for concern for long-term harms, including risk for cardiovascular disease, chronic obstructive lung disease, and cancer. Rather than helping people stop smoking, e-cigarette use is associated with reduced rates of smoking cessation among current smokers and an increased risk of relapse to smoking among former smokers. The World Health Organization advises, "Unlike the tried and tested nicotine and non-nicotine pharmacotherapies that are known to help people quit tobacco use, WHO does not endorse e-cigarettes as cessation aids." Careful evaluation of all the available research justifies a strong recommendation that healthcare providers should neither prescribe nor recommend e-cigarettes for persons who are tobacco dependent. If a patient is dependent on e-cigarettes, the healthcare provider should provide counseling and treatment (of nicotine dependence) to help the patient to stop their e-cigarette use.

Nicotine dependence treatment: provision of a dedicated programme by the National Addictions Management Service.

Smoking is the top cause of death among lifestyle habits and continues to affect more than one billion people around the world. The current gold standard for smoking cessation is a combination of pharmacological and behavioural approaches. In March 2017, the National Addictions Management Service, Singapore, initiated a smoking cessation programme that combined the pharmacological treatment options of either nicotine replacement therapy, bupropion or varenicline with individual counselling to achieve optimal results. Treatment is customised to the individual based on demographics, individual preferences, cost considerations, and history of chronic medical or psychiatric ailments. After more than 1.5 years of running this programme, we share the lessons learnt.

Mitigating Effects of Liriope platyphylla on Nicotine-Induced Behavioral Sensitization and Quality Control of Compounds

In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, back to normal levels, and increases the expression of dopamine transporter (DAT) protein, which is reduced by nicotine, back to normal levels in PC12 cells. In this study, rats received nicotine (0.4 mg/kg, subcutaneously) only for seven days and then received extract of L. platyphylla (200 or 400 mg/kg, oral) 1 h prior to nicotine administration for an additional seven days. The extract of L. platyphylla reduced locomotor activity compared to the nicotine control group in rats. The extract of L. platyphylla significantly attenuated the repeated nicotine-induced DAT protein expression in the nucleus accumbens (NAc), but there was no effect on increased TH protein expression in the dorsal striatum. These findings suggest that L. platyphylla extract has a mitigating effect on nicotine-induced behavioral sensitization by modulating DAT protein expression in the NAc. For quality control of L. plathyphylla, spicatoside A and D, which are saponin compounds, were quantified in the L. platyphylla extract. The amounts of spicatoside A and D in L. platyphylla extract obtained from ultra-high-performance liquid chromatography with tandem mass spectrometry were 0.148 and 0.272 mg/g, respectively. The identification of these compounds in L. platyphylla, which can be used for quality control, provides important information for the development of drugs to treat nicotine dependence.

Factors associated with nicotine dependence in a Brazilian rural town

Abstract Introduction Nicotine dependence is a serious global health issue. Over a billion people are estimated to smoke in the world. Withdrawing from smoking contributes significantly to reducing morbimortality. Low income, poor education and smoking from a young age are some of the factors that contribute to the prevalence of tobacco use and to smoking cessation. In Brazil, the National Programme of Tobacco Control is responsible for helping smokers undergoing treatment in primary care units. Objective To highlight the association between the results of a nicotine dependence treatment in a Brazilian town, its sociodemographic factors and smoking habits of patients. Methodology A cross-sectional study in Santa Cecília, Paraíba, a town in the northeast of Brazil in 2016, relying on data from the medical history of 85 smokers who received treatment in primary care units. Dropout rates and successful results were both considered. Pearson's chi-squared test with 95% significance level was used to assess the association between variables. Results 51.8% of patients quit smoking while 37.6% abandoned treatment. Around 4.7% of patients smoked fewer cigarettes after treatment and 5.9% did not have a successful result. Among the successful cases, the majority were women (54.4%). Considering smoking habits of those who quit smoking, the following was observed: 29.4% smoked 20 cigarettes per day, 27% were highly dependent on nicotine, 33% spent 20 to 40 years smoking and 18.9% underwent nicotine replacement therapies. Income, marital status and number of cigarettes were variables that showed significant differences (p < 0.001) after treatment. Conclusions Smoking cessation after treatment indicates the effectiveness of the programme. The engagement of healthcare professionals is paramount to successfully implement such treatments in primary health care. Further qualitative research is recommended to investigate other Brazilian cities and to assess patient progress individually. Key messages This work analyses factors related to nicotine dependence in groups of smokers undergoing treatment developed by the National Programme of Tobacco Control in a Brazilian rural town. Analysing the prevalence of smoking cessation and its related factors among patients undergoing treatment by the National Programme of Tobacco Control in a Brazilian rural town.

Smoking cessation.

Although Australia is a world leader in tobacco control, smoking remains the behavioural risk factor making the largestcontribution to death and disease. Smoking rates remain high in Aboriginal and Torres Strait Islander people and in people with mental health problems. Priority groups for cessation include women who are pregnant and people with cardiovascular disease. This article, based on the recently published second edition of Supporting smoking cessation: A guide for health professionals, provides an update on current evidence-based practice to support quitting. A brief, time-efficient intervention approach (Ask, Advise, Help) is proposed. New approaches to the use of pharmacotherapy are covered, as is the controversial role of nicotine-containing e-cigarettes and advice for groups with high smoking prevalence and those with special needs. A combination of behavioural support along with pharmacotherapy to treat nicotine dependence maximises the chances of successful long-term cessation. Combination nicotine replacement therapy (patch and short-acting oral form) or varenicline are the most effective forms of pharmacotherapy.

Inhibition of monoacylglycerol lipase reduces nicotine reward in the conditioned place preference test in male mice

Nicotine, the primary psychoactive component in tobacco, plays a major role in the initiation and maintenance of tobacco dependence and addiction, a leading cause of preventable death worldwide. An essential need thus exists for more effective pharmacotherapies for nicotine-use cessation. Previous reports suggest that pharmacological and genetic blockade of CB1 receptors attenuate nicotine reinforcement and reward; while exogenous agonists enhanced these abuse-related behaviors. In this study, we utilized complementary genetic and pharmacologic approaches to test the hypothesis that increasing the levels of the endocannabinoid 2-arachindonoylglycerol (2-AG), will enhance nicotine reward by stimulating neuronal CB1 receptors. Contrary to our hypothesis, we found that inhibition of monoacylglycerol lipase (MAGL), the primary catabolic enzyme of 2-AG, attenuates nicotine conditioned place preference (CPP) in mice, through a non-CB1 receptor-mediated mechanism. MAGL inhibition did not alter palatable food reward or Lithium Chloride (LiCl) aversion. In support of our findings, repeated MAGL inhibition did not induce a reduction in CB1 brain receptor levels or hinder function. To explore the potential mechanism of action, we investigated if MAGL inhibition affected other fatty acid levels in our CPP paradigm. Indeed, MAGL inhibition caused a concomitant decrease in arachidonic acid (AA) levels in various brain regions of interest, suggesting an AA cascade-dependent mechanism. This idea is supported by dose-dependent attenuation of nicotine preference by the selective COX-2 inhibitors valdecoxib and LM-4131. Collectively, these findings, along with our reported studies on nicotine withdrawal, suggest that inhibition of MAGL represents a promising new target for the development of pharmacotherapies to treat nicotine dependence.

Smoking cues impair monitoring but not stopping during response inhibition in abstinent male smokers

The attenuated inhibitory control of smokers is a stumbling block for treating nicotine dependence. Unfortunately, smokers are often exposed to cigarette-related salient cues, which may violate homeostasis, override self-control, and lead to relapse. To understand the mechanisms underlying these associations, we investigate the cognitive and neural processes of inhibitory control (including proactive and reactive inhibition) of smoking cues in abstinent smokers. Twenty-six smokers completed cue-reactivity and stop signal tasks during functional magnetic resonance imaging scans, on two separate sessions, 2–3 weeks apart: one involved a neutral cue reactivity task, and the other a smoking cue reactivity task. Findings pointed to no significant subjective craving changes, or behavioral influences of smoking cues on proactive and reactive inhibition. However, abstinent smokers exhibited hyperactive brain reactivity in response to smoking versus neutral stimuli, in regions including the insula, amygdala, anterior cingulate cortex (ACC), and putamen. They also had hypoactive bilateral rostral ACC (rACC) and hyperactive right pre-supplementary motor area during reactive inhibition in smoking versus neutral conditions. Support vector regression analysis showed that activation of these regions predicted and correlated with reactive inhibition index (i.e., SSRT), alluding to the possibility of their involvement in the reactive inhibition. Subjective craving scores were predicted by and correlated with activation of bilateral dorsal and rostral ACC, supporting the ideas of their possible involvement in subjective craving. These findings suggest that smoking cues evoke hyperactive brain reactivity; this may interfere with normal performance monitoring and rapid reactive inhibition. These findings have important implication for treating smoking dependence.

Intrinsic differences in insular circuits moderate the negative association betweennicotine dependence andcingulate-striatal connectivity strength.

The development of brain-based biomarkers to assess nicotine dependence severity and treatment efficacy are essential to improve the current marginally effective treatment outcomes. Cross-sectional resting state functional connectivity (rsFC) studies in humans identified a circuit between the dorsal anterior cingulate cortex and the ventral striatum that negatively correlated with increased nicotine dependence severity but was unaffected by acute nicotine administration, suggesting a trait marker of addiction. However, whether this trait circuit dysregulation is predispositional to or resultant from nicotine dependence is unclear. Using a rat model of nicotine dependence with longitudinal fMRI measurements, we assessed the relationship between ACC-striatal rsFC and nicotine dependence severity. Data-driven modularity-based parcellation of the rat medial prefrontal cortex (mPFC) combined with seed-based connectivity analysis with the striatum recapitulated the cingulate-striatum relationship observed in humans. Furthermore, the relationship between cingulate-striatal brain circuits and nicotine dependence severity as indexed by the intensity of precipitated withdrawal, was fully statistically moderated by a predispositional insular-frontal cortical functional circuit. These data suggest that the identified trans-species ACC-striatal circuit relationship with nicotine dependence severity is dysregulated following chronic nicotine administration-induced dependence and may be biased by individual differences in predispositional insula-based striatal-frontal circuits, highlighting the circuit's potential as a biomarker of dependence severity.

Verbal suggestions of nicotine content modulate ventral tegmental neural activity during the presentation of a nicotine-free odor in cigarette smokers

Expectancies of nicotine content have been shown to impact smokers’ subjective responses and smoking behaviors. However, little is known about the neural substrates modulated by verbally induced expectancies in smokers. In this study we used functional magnetic resonance imaging (fMRI) to investigate how verbally induced expectations, regarding the presence or absence of nicotine, modulated smokers’ neural response to a nicotine-free odor. While laying in the scanner, all participants (N = 24) were given a nicotine-free odor, but whereas one group was correctly informed about the absence of nicotine (control group n = 12), the other group was led to believe that the presented odor contained nicotine (expectancy group n = 12). Smokers in the expectancy group had significantly increased blood-oxygen-level-dependent (BOLD) responses during the presentation of the nicotine-free odor in the left ventral tegmental area (VTA), and in the right insula, as compared to smokers in the control group (Regions of interest analysis with pFWE-corrected p ≤ 0.05). At a more liberal uncorrected statistical level (p-unc ≤ 0.001), increased bilateral reactivity in the dorsolateral prefrontal cortex (dlPFC) was also observed in the expectancy group as compared with the control group. Our findings suggest that nicotine-expectancies induced through verbal instructions can modulate nicotine relevant brain regions, without nicotine administration, and provide further neural support for the key role that cognitive expectancies play in the cause and treatment of nicotine dependence.

SNPs within CHRNA5-A3-B4 and CYP2A6/B6, nicotine metabolite concentrations and nicotine dependence treatment success in smokers.

Plasma values of nicotine and its metabolites are highly variable, and this variability has a strong genetic influence. In our study, we analysed the impact of common polymorphisms associated with smoking on the plasma values of nicotine, nicotine metabolites and their ratios and investigated the potential effect of these polymorphisms and nicotine metabolite ratios on the successful treatment of tobacco dependence. Five variants (rs16969968, rs6474412, rs578776, rs4105144 and rs3733829) were genotyped in a group of highly dependent adult smokers (n=103). All smokers underwent intensive treatment for tobacco dependence; 33 smokers were still abstinent at the 12-month follow-up. The rs4105144 (CYP2A6, P<0.005) and rs3733829 (EGLN2, P<0.05) variants were significantly associated with plasma concentrations of 3OH-cotinine and with 3OH-cotinine: cotinine ratios. Similarly, the unweighted gene score was a significant (P<0.05) predictor of both cotinine:nicotine and 3OH-cotinine:cotinine ratios. No associations between the analysed polymorphisms or nicotine metabolite ratios and nicotine abstinence rate were observed. Although CYP2A6 and EGLN2 polymorphisms were associated with nicotine metabolism ratios, neither these polymorphisms nor the ratios were associated with abstinence rates.

The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments

The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments

Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence.

Both types of cannabinoid receptors-CB1 and CB2 -regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs. Δ9 -Tetrahydrocannabivarin (Δ9 -THCV)-a cannabis constituent-acts as a CB1 antagonist and a CB2 agonist. Δ8 -Tetrahydrocannabivarin (Δ8 -THCV) is a Δ9 -THCV analogue with similar combined CB1 antagonist/CB2 agonist properties. We tested Δ8 -THCV in seven different rodent models relevant to nicotine dependence-nicotine self-administration, cue-triggered nicotine-seeking behaviour following forced abstinence, nicotine-triggered reinstatement of nicotine-seeking behaviour, acquisition of nicotine-induced conditioned place preference, anxiety-like behaviour induced by nicotine withdrawal, somatic withdrawal signs induced by nicotine withdrawal, and hyperalgesia induced by nicotine withdrawal. Δ8 -THCV significantly attenuated intravenous nicotine self-administration and both cue-induced and nicotine-induced relapse to nicotine-seeking behaviour in rats. Δ8 -THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice. We conclude that Δ8 -THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.

Behavior and Hippocampal Epac Signaling to Nicotine CPP in Mice.

Tobacco use is a major challenge to public health in the United States and across the world. Many studies have demonstrated that adult men and women differ in their responses to tobacco smoking, however neurobiological studies about the effect of smoking on males and females were limited. Exchange protein directly activated by cAMP (Epac) signaling participates in drug addictive behaviors. In this study, we examined the hippocampal Epac signaling in nicotine-induced place conditioning mice. Nicotine at 0.2 mg/kg and 0.4 mg/kg induced a conditioned place preference (CPP) in male and female mice, respectively. After CPP, male mice presented less anxiety-like behavior as demonstrated by an open-field test. The hippocampal Epac2 protein was elevated in both male and female nicotine place conditioning mice. However, Rap1 protein was elevated and CREB phosphorylation was reduced in female nicotine place conditioning mice. Our data provide direct evidence that hippocampal Epac signaling is altered in nicotine-induced CPP mice. Pharmacology manipulation Epac signaling may open a new avenue for the treatment of nicotine abuse and dependence.

Targeting Orexin to Treat Nicotine Dependence

Targeting Orexin to Treat Nicotine Dependence

Efficacy of Varenicline in Patients With Severe Alcohol Dependence: A Pilot Double-Blind Randomized and Controlled Study.

Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification. We conducted a phase II, double-blind, placebo-controlled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking). Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not show a significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group. In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed.

The Impact of Family and Social Support during the First Six Months after Attempt for Smoking Cessation

Objective: The aim of the present study was to investigate the effect of family and social support on smoking cessation during the first six months after the cessation attempt. Methods: The files of 312 patients who were admitted to the Smoking Cessation Outpatient Clinic of Family Medicine Department, Ondokuz Mayıs University Faculty of Medicine between January 2011 and January 2012 were reviewed and their socio-demographic data, smoking characteristics, Fagerström Nicotine Dependence Test (FNDT) score and treatment methods were recorded. Participants were called in a five-minute structured interview and their quit rate was investigated. They were also evaluated for the support they received from the family and social environment during the cessation period with a ten-point Likeert Scale (0 = Never, 10= Excellent) Findings: Of the cases, 190 (61%) were male and 122 (39%) were female. While the mean FNBT score of the group was 5.1 ± 1.7 , the package / year value was 22.3 ± 18.7. Forty four out of 209 participants (21%) who were started medication (Varenicline or Bupropion) and 23 out of 127 participants (%18%) who were started Nicotine Replacement Therapy (NRT) had been smoking for six months. There was not a statistically significant difference between genders with regard to overall social and family support scores (male = 41,3 ± 15,3, female = 44,4 ± 16,0, t = 1,495, p = 0,136). According to a multivariate binary logistic regression model, overall social and family support score (OR = 1,044), age (OR= -1,038), and presence of another smoker family member (OR =0,501) were found as independent factors on smoking cessation. Conclusion: Family and social support are important factors for both gender during making a decision for smoking cessation, during smoking cessation and after smoking cessation and detailed studies are needed.Amaç: Bu araştırmada sigara bırakma denemesine karar verme ve sonraki ilk altı aylık dönemde sigara bırakma üzerine aile ve sosyal çevreden alınan desteğin etkisinin araştırılması hedeflenmiştir. Araç ve Yöntem: Ondokuz Mayıs Üniversitesi Tıp Fakültesi Aile Hekimliği Sigara Bıraktırma Polikliniği’ne Ocak 2011-Ocak 2012 tarihleri arasında başvuran 312 kişinin dosyaları taranarak kişilerin sosyodemografik verileri, sigara kullanma özellikleri, Fagerstrom Nikotin Bağımlılık Testi (FNBT) skoru ve aldıkları tedavi yöntemleri not edilmiştir. Bu kişiler telefonla aranarak beş dakikalık yapılandırılmış bir görüşme gerçekleştirilmiş ve sigarayı bırakma oranları araştırılmıştır. Görüşmede ayrıca sigara bırakma aşamasında ve sigarayı bırakırken aileden ve sosyal çevreden aldıkları destek onlu bir Likert Skala ile değerlendirilmiştir (0=Hiç, 10=Mükemmel). Bulgular: Çalışmaya alınanların 190’ı (% 61) erkek, 122’si (%39) kadındı. Grubun ortalama FNBT skoru 5,1±1,7 iken paket/yıl değeri 22,3±18,7 idi. İlaç (Vareniklin veya Bupropion) tedavisi başlanan 209 katılımcının 44’ü (%21), Nikotin Replasman Tedavisi (NRT) başlanan 127 katılımcının 23’ü (%18) altı aydır sigara içmiyordu (x2=0,283, p=0,868). Her iki cinsiyetin aldığı toplam sosyal destek ve aile desteği puanları birbirinden istatistiksel olarak anlamlı değildi (erkekler= 41,3±15,3, kadınlar= 44,4±16,0, t=1,495, p=0,136). Multivariate binary logistic regression modeline göre toplam sosyal ve ailesel destek puanı (OR= 1,044), yaş (OR= -1,038) ve sigara bağımlısının evinde başka birinin daha sigara içmemesi (OR= -0,501) sigara bırakma üzerinde bağımsız faktörler olarak bulunmuştur. Sonuç: Sigara bırakma kararı alma, bırakma esnasında ve bırakma sonrasında aile desteği ve sosyal destek her iki cinsiyet için önemli bir faktördür ve bu konuda detaylı araştırmalara ihtiyaç vardır.

Smoke cessation in cardiovascular pathology from the perspective of evidence-based medicine

The effectiveness of smoking cessation methods has been studied in various studies. However, little is known about the peculiarities of treatment of nicotine dependence in patients with cardiovascular diseases. In the presented review, according to the literature, the prevalence and characteristics of smoking, the duration of abstinence from smoking in patients with cardiovascular diseases with different methods of quitting tobacco use are described.It is shown that smoking cessation not only shows long-term positive effects, but almost immediately the supply of cells with oxygen increases, platelet aggregation, fibrinogen synthesis decreases. Carrying out treatment for nicotine addiction, especially when combined with behavioral support, significantly increases the effectiveness of quitting smoking. With the cardiovascular pathology, the efficacy and safety of varenicline has been proven.

Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats.

Simultaneous alcohol and nicotine consumption occurs in the majority of individuals with alcohol use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclinical research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake. Animals were randomly assigned to one of four drinking conditions of 24-h access to a three-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14mg/mL NIC (EtOH+NIC). The effects of Var (0, 1, or 2mg/kg) or Nal (0, 1, or 10mg/kg) injections on maintenance and relapse consumption were determined during four consecutive days. Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking. The results indicate the standard pharmacological treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.

Brief Report: Rate of Nicotine Metabolism and Tobacco Use Among Persons With HIV: Implications for Treatment and Research.

The nicotine metabolite ratio (NMR) is a biomarker that represents individual variation in the speed that nicotine is metabolized. The rate of nicotine metabolism alters smoking behavior (eg, amount) and has been validated for personalizing tobacco dependence medication selection to increase treatment efficacy and reduce treatment side effects in the general population of smokers. Although smoking rates are extremely high among those with HIV, the NMR has not been evaluated in this underserved population. We used baseline data from a smoking cessation clinical trial for smokers with HIV (N = 131) to examine associations between NMR and demographic, smoking, disease-related, and psychological characteristics. Pearson r and analysis of variance were used to identify univariate correlates of NMR, which were then entered into a multiple linear regression model. In univariate analyses, a higher NMR (faster nicotine metabolism) was associated with being white, and more cigarettes per day, nicotine dependence, exhaled carbon monoxide, and symptoms of depression and anxiety, and using efavirenz. In a multiple regression model, a higher NMR was associated with more cigarettes per day, higher anxiety symptoms, and efavirenz use. As in other populations, faster nicotine metabolism was associated with the use of more cigarettes and higher anxiety symptoms. Notably, efavirenz use was associated with faster metabolism, which might make it harder to quit smoking for people with HIV treated with that medication. These findings could help guide further study and the clinical use of the NMR to personalize nicotine dependence treatment in this underserved population.

Potent Dopamine D2 Antagonists Block the Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia.

Antipsychotics that are potent dopamine (DA) D2 receptor antagonists have been linked to elevated levels of nicotine dependence in smokers with schizophrenia. Because activation of D2 receptors mediates motivation for nicotine, we examined whether potent D2 antagonists would diminish nicotine's ability to stimulate reward processing-a mechanism that may drive compensatory increases in smoking. Smokers with schizophrenia (n = 184) were recruited and stratified into medication groups based on D2 receptor antagonist potency. The effects of smoking on reward function were assessed using a probabilistic reward task (PRT), administered pre- and post-smoking. The PRT used an asymmetrical reinforcement schedule to produce a behavioral response bias, previously found to increase under conditions (including smoking) that enhance mesolimbic DA signaling. Among the 98 participants with valid PRT data and pharmacotherapy that could be stratified into D2 receptor antagonism potency, a medication × smoking × block interaction emerged (P = .005). Post-hoc tests revealed a smoking × block interaction only for those not taking potent D2 antagonists (P = .007). This group exhibited smoking-related increases in response bias (P < .001) that were absent in those taking potent D2 antagonists (P > .05). Our findings suggest that potent D2 antagonists diminish the reward-enhancing effects of nicotine in smokers with schizophrenia. This may be a mechanism implicated in the increased rate of smoking often observed in patients prescribed these medications. These findings have important clinical implications for the treatment of nicotine dependence in schizophrenia.