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Introduction Nicotine and tobacco smoking administration have demonstrated antinociceptive effects that are mediated by the nicotinic acetylcholine receptor containing the beta2* subunit (beta(2)*-nAChR). In this study, we examined the relationship between beta(2)*-nAChR availability and nociception during acute withdrawal in human tobacco smokers using [(123)I]5-IA-85380 ([(123)I]5-IA) and single photon emission computed tomography (SPECT) brain imaging. Methods Tobacco smokers (n = 24, aged 34 +/- 11 years) participated in the cold pressor task during acute withdrawal (up to 3 hr) and a second cold pressor task following 7-13 days of smoking abstinence on the day they were imaged with [(123)I]5-IA SPECT. The cold pressor task is used to measure pain sensitivity (when subjects first feel pain) and pain tolerance (when subjects cannot withstand pain). Results Following 7-13 days of tobacco smoking abstinence, increased pain sensitivity, for example, shorter time to first feel pain, was significantly associated with higher beta(2)*-nAChR availability in the thalamus (r = -.43), parietal (r = -.50), frontal (r = -.55), anterior cingulate (r = -.44), temporal (r = -.43), and occipital (r = -.48) cortices. The percent change in pain sensitivity from the first to second cold pressor task was significantly correlated with beta(2)*-nAChR availability in the thalamus (r = -.57), cerebellum (r = -.50), striatum (r = -.057), parietal (r = -.46), anterior cingulate (r = -.48), temporal (r = -.55), and occipital (r = -.57) cortices. Similar associations were not observed with pain tolerance. Discussion This suggests that beta(2)*-nAChRs play a role in pain sensitivity but not pain tolerance during tobacco smoking withdrawal. If individuals are more likely to relapse in response to painful stimuli, lower beta(2)*-nAChR availability during acute abstinence may be protective.

INTRODUCTION Given the prevalence of alcohol use among adolescents and its negative consequences, it is important to learn more about correlates of alcohol-related problems in this population. Cigarette smoking appears to be associated with alcohol-related problems in adolescents. The purpose of this study was to assess cigarettes smoked per day and nicotine dependence (ND) severity as predictors of alcohol-related problems in cross-sectional models, using data from a smoking cessation clinical trial for adolescents. METHOD Data obtained at intake were used to assess smoking-related variables as cross-sectional predictors of alcohol-related problems in models along with drinks per week and key demographics, using hierarchical multiple regression. RESULTS ND severity, as measured using the modified Fagerstrom Tolerance Questionnaire, significantly predicted alcohol-related problems, both when this score included and did not include an item concerning cigarettes smoked per day. A separate continuous item capturing cigarettes per day did not predict alcohol-related problems. DISCUSSION ND severity predicted alcohol-related problems in cross-sectional regression models, holding constant alcohol consumption and key demographics. This suggests that ND severity may be a clinical indicator of alcohol-related problems among adolescent smokers. To our knowledge, this is the first analysis of associations between smoking and alcohol involvement in a sample of adolescent smokers participating in a clinical trial.

Background Although shopping behavior among adolescents is normal, for some, the shopping becomes problematic. An assessment of adolescent shopping behavior along a continuum of severity and its relationship to other behaviors and health issues is incompletely understood. Methods A large sample of high school students (n = 3999) was examined using a self-report survey with 153 questions concerning demographic characteristics, shopping behaviors, other health behaviors including substance use, and functioning variables such as grades and violent behavior. Results The overall prevalence of problem shopping was 3.5% (95% CI, 2.93-4.07). Regular smoking, marijuana and other drug use, sadness and hopelessness, and antisocial behaviors (e.g., fighting, carrying weapons) were associated with problem shopping behavior in both boys and girls. Heavy alcohol use was significantly associated with problem shopping only in girls. Conclusion Problem shopping appears fairly common among high school students and is associated with symptoms of depression and a range of potentially addictive and antisocial behaviors. Significant distress and diminished behavioral control suggest that excessive shopping may often have significant associated morbidity. Additional research is needed to develop specific prevention and treatment strategies for adolescents who report problems with shopping.

Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which may contribute to relapse. We hypothesized that cortical gamma aminobutyric acidA-benzodiazepine receptor (GABAA-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABAA-BZRs were imaged in 15 smokers (8 men and 7 women), and 15 healthy age and sex-matched nonsmokers, and 4 abstinent tobacco smokers (3 men; 1 woman) using [123I]iomazenil and single photon emission computed tomography (SPECT). Anxiety and depressive symptoms were measured using the Spielberger's State-Trait Anxiety Index (STAI) and the Center for Epidemiology Scale for Depressive Symptoms (CES-D). The cold pressor task was administered to assess pain tolerance and sensitivity. The relationship between cortical GABAA-BZR availability, smoking status, and subsyndromal depression and anxiety symptoms, as well as pain tolerance and sensitivity, were evaluated. Surprisingly, there were no statistically significant differences in overall GABAA-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABAA-BZR availability negatively correlated with subsyndromal state anxiety symptoms in nonsmokers but not in smokers. In nonsmokers, the correlation was seen across many brain areas with state anxiety [parietal (r = −0.47, P = 0.03), frontal (r = −0.46, P = 0.03), anterior cingulate (r = −0.47, P = 0.04), temporal (r = −0.47, P = 0.03), occipital (r = −0.43, P = 0.05) cortices, and cerebellum (r = −0.46, P = 0.04)], trait anxiety [parietal (r = −0.72, P = 0.02), frontal (r = −0.72, P = 0.02), and occipital (r = −0.65, P = 0.04) cortices] and depressive symptoms [parietal (r = −0.68; P = 0.02), frontal (r = −0.65; P = 0.03), anterior cingulate (r = −0.61; P = 0.04), and temporal (r = −0.66; P = 0.02) cortices]. The finding that a similar relationship between GABAA-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABAA-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABAA-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABAA-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression. Synapse 63:1089–1099, 2009. © 2009 Wiley-Liss, Inc.

Context Available levels of nicotinic acetylcholine receptors containing the β 2 subunit (β 2 *-nAChR) are higher in recently abstinent tobacco smokers compared with participants who never smoked. Variations in β 2 *-nAChR availability during the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal, and successful abstinence. Objective To examine changes in β 2 *-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in β 2 *-nAChR availability were related to clinical features of tobacco smoking. Design Tobacco smokers participated in up to 4 iodide 123–labeled 5-iodo-A-85380 ([ 123 I]5-IA) single-photon emission computed tomography (SPECT) scans during abstinence at 1 day (n = 7) and 1 (n = 17), 2 (n = 7), 4 (n = 11), and 6 to 12 (n = 6) weeks. Age-matched nonsmokers participated in a single [ 123 I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Setting Academic imaging center. Participants Tobacco smokers (n = 19) and an age-matched nonsmoker comparison group (n = 20). Main Outcome Measure The [ 123 I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. Results Compared with nonsmokers, β 2 *-nAChR availability in the striatum, cortex, and cerebellum of smokers was not different at 1 day of abstinence, was significantly higher at 1 week of abstinence, and was not different at 4 or at 6 to 12 weeks of abstinence. In smokers, β 2 *-nAChR availability was significantly lower in the cortex and cerebellum at 6 to 12 weeks compared with 1 week of abstinence. In addition, cerebellar β 2 *-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of the SPECT scan. Conclusions These data suggest that higher β 2 *-nAChR availability persists up to 1 month of abstinence and normalizes to nonsmoker levels by 6 to 12 weeks of abstinence from tobacco smoking. These marked and persistent changes in β 2 *-nAChR availability may contribute to difficulties with tobacco cessation.

Contingency management (CM) is a powerful behavioral intervention that has been shown to reduce the use of a wide variety of substances including tobacco. Use of CM techniques for smoking cessation has been restricted by the use of multiple daily measurements of breath CO as the objective indicator to reinforce abstinence. Cotinine, with its longer half-life, may be a better marker. We evaluated the use of urine cotinine (determined using once-daily semiquantitative Immunoassay Test Strips and verified using quantitative GC/HPLC techniques) as an abstinence indicator in treatment seeking adult and adolescent smokers participating in a CM-based intervention program. The results indicate that both techniques of determining urine cotinine were highly sensitive and moderately specific at detecting abstinence, and were highly concordant. However, specificity was somewhat lower during the first few days of a quit attempt and improved over time. The results were similar in adults and adolescent smokers and suggest that during the first few days of a quit attempt it would be advisable to continue to use daily multiple CO measurements to verify abstinence. However, once abstinence is achieved, once daily immunoassay test strips could be used for continued monitoring of urine cotinine levels. Immunoassay testing can identify individuals who relapse to smoking, though this study cannot evaluate whether the strips can identify resumption of abstinence. These results suggest that the use of cotinine as an abstinence indicator, by reducing the number of daily appointments, could significantly enhance the feasibility and utility of CM-based interventions for smoking cessation.

An inability to maintain abstinence is a key indicator of tobacco dependence. Unfortunately, little evidence exists regarding the ability of the major tobacco dependence measures to predict smoking cessation outcome. This paper used data from four placebo-controlled smoking cessation trials and one international epidemiologic study to determine relations between the Fagerstrom Test for Nicotine Dependence (FTND; Heatherton et al., 1991), the Heaviness of Smoking Index (HSI; Kozlowski et al., 1994), the Nicotine Dependence Syndrome Scale (NDSS; Shiffman et al., 2004) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM; Piper et al. 2004) with cessation success. Results showed that much of the predictive validity of the FTND could be attributed to its first item, time to first cigarette in the morning, and this item had greater validity than any other single measure. Thus, the time to first cigarette item appears to tap a pattern of heavy, uninterrupted, and automatic smoking and may be a good single-item measure of nicotine dependence.

This pilot study evaluated the optimal format of cognitive behavioral therapy (CBT) to combine with contingency management (CM) in a four-week, high school-based smoking cessation program. Thirty-four adolescent smokers received a standard weekly version of CBT or a frequent brief behavioral intervention. Results indicate a trend toward a higher seven-day point prevalence end-of-treatment abstinence rate and percent days abstinent during treatment in the CBT condition. In addition, significantly more participants in the CBT group completed treatment. These preliminary results suggest that when combined with CM, the standard weekly format of CBT is more acceptable to adolescent smokers.

We examined subjective responses to smoking the first cigarette of the day and investigated how these responses related to smoking cessation treatment outcome. Data from participants (N = 207) in a clinical trial of message framing for smoking cessation with bupropion, obtained prior to the targeted quit day, were used to examine indices of craving, withdrawal, and affect before and after smoking the first cigarette of the day. After smoking the initial cigarette, craving, withdrawal symptoms, and negative affect were lessened, and positive affect increased. Greater decreases in craving as measured by the questionnaire on smoking urges-brief (QSU-Brief) predicted relapse at the end of treatment (6 weeks) and at the 3-month follow-up time point. These associations do not appear to be mediated by established measures of dependence. Thus, this preliminary study provides evidence that there are significant changes in craving, withdrawal, and affect related to smoking the first cigarette of the day, with the largest of these changes observed for craving. Moreover, changes in tobacco craving in response to the first cigarette of the day may be a novel predictor of smoking relapse that should be tested in future studies.

Background The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH−) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. Methods Ninety-two, non–treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. Results Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers ( n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH− drinkers. Conclusions These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking.

Nicotine, the addictive chemical in tobacco smoke, initiates its actions in brain through nicotinic acetylcholine receptors (nAChRs). In particular, nAChRs containing β2-subunits (β2*-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine. We hypothesized that abnormal numbers of β2*-nAChRs during early abstinence contribute to the perpetuation of addiction to tobacco smoking. Using molecular imaging, specifically single-photon emission computed tomography with the nAChR agonist radiotracer [123I]5-IA-85380 ([123I]5-IA), we imaged β2*-nAChR availability in human smokers. First, using nonhuman primates treated chronically with nicotine, we estimated the time interval necessary for smokers to abstain from smoking so that residual nicotine would not interfere with [123I]5-IA binding to the β2*-nAChR as ∼7 d. Thus, we imaged human smokers at 6.8 ± 1.9 d (mean ± SD) of abstinence. Abstinence was confirmed by daily assessments of urinary cotinine and expired carbon monoxide levels. In smokers, [123I]5-IA uptake was significantly higher throughout the cerebral cortex (26–36%) and in the striatum (27%) than in nonsmokers, suggesting higher β2*-nAChR in recently abstinent smokers. β2*-nAChR availability in recently abstinent smokers correlated with the days since last cigarette and the urge to smoke to relieve withdrawal symptoms but not the severity of nicotine dependence, severity of nicotine withdrawal, or the desire to smoke. Higher brain β2*-nAChR during early abstinence indicates that, when smokers quit smoking, they do so in the face of a significant increase in the receptors normally activated by nicotine. Greater β2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence.

This pilot study evaluated the use of contingency management (CM) procedures in combination with cognitive-behavioral therapy (CBT) for smoking cessation in adolescents. Twenty-eight treatment-seeking adolescent smokers participated in a 1-month, school-based smoking cessation program and were randomly assigned to receive either CM with weekly CBT or CBT alone. In the CM+CBT group, biochemical verification of abstinence was obtained twice daily during the first 2 weeks, followed by daily appointments during the 3rd week and once every other day during the 4th week. Participants were monetarily reinforced for abstinence on an escalating magnitude schedule with a reset contingency. At the end of 1 week and 1 month of treatment, abstinence verified using quantitative urine cotinine levels was higher in participants in the CM+CBT group (1 week: 76.7%; 1 month: 53.0%) when compared with the CBT-alone group (1 week: 7.2%; 4 weeks: 0%). These preliminary results provide a strong initial signal supporting the utility of CM techniques for smoking cessation in adolescents and demonstrate the feasibility of implementing such a program in a school setting.

As smoking rates in the general population continue to fall in response to new information and changing social values, the continued high rate of smoking among persons with psychiatric disorders has caught the attention of society at many levels: public health officials, medical and mental health care providers, and concerned family members alike. As a consequence, research studies aimed at quantifying the problem and understanding its cause have increased dramatically over the past several years. The following review first examines epidemiological studies that have revealed a bidirectional causal relationship between tobacco dependence and posttraumatic stress disorder (PTSD), one of several mental health disorders in which tobacco dependence remains prevalent and resistant to intervention. Second, we use a translational neuroscience perspective to discuss possible neurobiological mediators of the relationship between PTSD and tobacco dependence, hoping to spur further human and animal research that will elucidate pathogenetic mechanisms involved and inspire novel treatment interventions. Finally, to enable more effective clinical research in this area, we provide an overview of effective scientific methods for assessing and managing ‘smoking status’ as an experimental variable in clinical research studies of PTSD as well as other mental health disorders.

Background Cigarette smoking rates in schizophrenia are higher than in the general population. Objectives To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking–related cognitive enhancement. Design Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d). Participants Twenty-five smokers with schizophrenia and 25 control smokers. Setting Outpatient mental health center. Main Outcome Measures Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores. Results In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment. Conclusions Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

Background Previous studies suggest that smokers minimize the personal health risk of smoking. Smokers may not be aware of the various smoking-related disease risks or believe that they are susceptible to them. Methods We presented 537 adult treatment-seeking smokers with a list of 34 medical conditions, of which 25 were smoking-related conditions, and 9 were nonsmoking-related items. Subjects were asked to identify which medical conditions were smoking-related, and to rate their perceived risk (using a 7-point Likert scale) of developing various smoking-related conditions if they continued to smoke. Results The average percentage of knowledge items correct for each disease category included cardiovascular (93%), pulmonary (94%), oral health diseases (89%), smoking-related cancers (71%), and reproductive risks (44%). Premature death was identified as a risk by 95% of smokers yet only 63.5% reported that disability could also result from smoking. Knowledge was associated with perceived risk of smoking-related illnesses across disease categories. Conclusions Knowledge and perceived risk of cardiovascular, pulmonary, and oral disease was high among current smokers; knowledge and perceived risk of reproductive-related problems, and cancers other than lung cancer was much lower. Smokers recognize that smoking may result in premature death, but are less likely to acknowledge that smoking could result in a disability significantly affecting their quality of life.

Timeline followback (TLFB) methodology was used to assess the daily use of cigarettes, alcohol, and marijuana in adolescent cigarette smokers and nonsmokers over the prior 30 days. Adolescent smokers reported more frequent daily use of both alcohol and marijuana than nonsmokers did. Of those smokers and nonsmokers who drank alcohol and used marijuana, smokers reported more frequent daily use of alcohol, but not marijuana. In examining daily use patterns, there were very few instances when adolescent smokers used alcohol but did not smoke cigarettes, and smokers used marijuana alone on more days than alcohol alone. One-fifth of the adolescent smokers used all three substances on the same day in the past month. There were no significant differences in the patterns of alcohol and marijuana use between female and male smokers, regardless of age. Implications for clinical interventions and future research are discussed.

This preliminary study evaluated the potential efficacy of 50 mg of the opioid antagonist naltrexone or placebo in combination with nicotine replacement therapy for smoking cessation, in a small sample of 32 smokers using one to one and a half packs of cigarettes per day. Addition of naltrexone resulted in an increase in continuous abstinence rates (9/16 for naltrexone vs. 5/16 for placebo). Naltrexone reduced the likelihood of relapse among participants who smoked during the first week of treatment, reduced desire to smoke, and prevented weight gain following smoking cessation. These preliminary results suggest that naltrexone augmentation of nicotine patch therapy using procedures designed to optimize the concurrent use of these two medications may be beneficial for smoking cessation.

Different vulnerabilities are launched or play a more active role at different developmental stages and different ages. Furthermore, the interplay between developmental and biological, psychosocial, and environmental vulnerabilities is expected to differ across stages of smoking. This article focuses on the intersection of vulnerability associated with adolescence with tobacco-use vulnerability resulting from biological, psychological, and environmental characteristics of an adolescent. Recommendations include the following: (a) Effectively treat childhood and adolescent behavioral and emotional disorders that place adolescents at risk; (b) target programs toward specific high-risk subgroups; (c) incorporate training in self-control, affect regulation, and healthy coping strategies into educational programs and extracurricular activities; (d) encourage youth to develop healthy sources of success and satisfaction; (e) encourage communities and states to launch environmental, policy, and regulatory initiatives to protect youth from tobacco; (f) consider bold initiatives that will require fundamental changes in public attitudes, including monetary rewards for nonsmoking, heightened penalties for facilitating and engaging in underage smoking, and government subsidies for substitute pharmacological agents.

Cigarette smoking is a leading cause of many adverse health consequences. Chronic nicotine exposure leads to insulin resistance and may increase the risk of developing non-insulin-dependent diabetes mellitus in young otherwise healthy smokers. To evaluate smoking-induced effects on carbohydrate metabolism, we studied muscle glycogen recovery from exercise in a young healthy population of smokers. The study used 31P-13C NMR spectroscopy to compare muscle glycogen and glucose 6-phosphate levels during recovery in exercised gastrocnemius muscles of randomized cohorts of healthy male smokers (S) and controls (C). Data for the two groups were as follows: S, ≥20 cigarettes/day ( n = 8), 24 ± 2 yr, 173 ± 3 cm, 70 ± 4 kg and age- and weight-matched nonsmoking C ( n = 10), 23 ± 1 yr, 175 ± 3 cm, 67 ± 3 kg. Subjects performed single-leg toe raises to deplete glycogen to ∼20 mmol/l, and glycogen resynthesis was measured during the first 4 h of recovery. Plasma samples were assayed for glucose and insulin at rest and during recovery. Test subjects were recruited from the general community surrounding Yale University. Glycogen was depleted to similar levels in the two groups [23.5 ± 1.2 (S) and 19.1 ± 1.3 (C) mmol/l]. During the 1st h of recovery, glycogen synthesis rates were similar [13.8 ± 1.1 (S) and 15.3 ± 1.3 (C) mmol·l-1·h-1]. Between hours 1 and 4, glycogen synthesis was impaired in smokers [0.8 ± 0.2 (S) and 4.5 ± 0.5 (C) mmol·l-1·h-1, P = 0.0002] compared with controls. Glucose 6-phosphate was reduced in smokers during hours 1–4 [0.105 ± 0.006 (S) and 0.217 ± 0.019 (C) mmol/l, P = 0.0212]. We conclude that cigarette smoking impairs the insulin-dependent portion of muscle recovery from glycogen-depleting exercise. This impairment likely results from a reduction in glucose uptake.

Study Design: • 8 focus groups (n=59;) with 18-25 year old young adults attending 2 public colleges in Connecticut. • Groups were stratified by gender (n=28 (55%) female) and smoking status (n=29 (49%) daily cigarette smokers; n=31 (51%) non-smokers). • A standard focus group guide was used to ask participants about their knowledge of MRTPs (electronic cigarettes and dissolvables) and usefulness in smoking cessation.

Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5-HT) levels in brain and may cause homeostatic adaptations in DA and 5-HT transporters. Since sex steroids alter DA and 5-HT transporter expression, the effects of smoking on DA and 5-HT transporter availability may differ between sexes. In the present study, DA and 5-HT transporter availabilities were quantitated using single photon emission computed tomography (SPECT) imaging approximately 22 h after bolus administration of [123I]β-CIT, an analog of cocaine which labels DA and 5-HT transporters. Forty-two subjects including 21 pairs of age-, race-, and gender-matched healthy smokers and nonsmokers (12 female and 9 male pairs) were imaged. Regional uptake was assessed by the outcome measures, V3″, which is the ratio of specific (i.e., ROI-cerebellar activity) to nondisplaceable (cerebellar) activity, and V3, the ratio of specific to free plasma parent. Overall, striatal and diencephalic [123I]β-CIT uptake was not altered by smoking, whereas brainstem [123I]β-CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]β-CIT uptake was higher in the striatum (10%), diencephalon (15%), and brainstem (15%) in females vs. males. The sex*smoking interaction was not significant in the striatum, diencephalon, or brainstem, despite the observation of 20% higher brainstem [123I]β-CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and nonsmokers. The results demonstrate higher DA and 5-HT transporter availability in females vs. males and no overall effect of smoking with the exception of a modest elevation in brainstem 5-HT transporters in male smokers. Although these findings are preliminary and need validation with a more selective 5-HT transporter radiotracer, the results suggest that brainstem 5-HT transporters may be regulated by smoking in a sex-specific manner. Synapse 41:275–284, 2001. © 2001 Wiley-Liss, Inc.

Naltrexone, an opiate antagonist, is well tolerated by most alcoholic patients; however, a subset reports significant nausea that can limit the effectiveness of this therapy. The goal of this study was to identify risk factors for naltrexone-precipitated nausea to assist in the development of management strategies to maximize the overall effectiveness of naltrexone. On the basis of the hypothesis that alterations in the endogenous opioid system occur with repeated stimulation of endogenous opioids by alcohol, the authors predicted that the recency and intensity of alcohol use would be related to the risk of naltrexone-induced nausea. One hundred twenty alcohol-dependent subjects participated in an open-label trial of naltrexone. After 5 to 30 days of abstinence, subjects received an initial naltrexone dose of 25 mg followed by a dose of 50 mg daily thereafter for 10 weeks. New-onset adverse effects were rated mild, moderate, or severe after 1 week of naltrexone. Logistic regression analyses were used to predict moderate to severe nausea during the first week of therapy from pretreatment patient characteristics. Moderate to severe nausea was reported by 18 subjects (15%) and was linked to poorer medication compliance and heavier drinking during treatment. Risk of nausea was significantly predicted by age, gender, intensity of drinking, duration of abstinence, and the interaction of abstinence duration and intensity of drinking. At shorter durations of abstinence, lighter drinkers were more likely to experience nausea than heavier drinkers. However, the risk of nausea declined with longer periods of abstinence, particularly for lighter drinkers. Younger age and female gender were associated with higher rates of nausea. These results support the hypothesis that recency and intensity of alcohol use are related to opiate antagonist-precipitated nausea and suggest that long-term alcohol use may result in alterations in the endogenous opioid system. Potential strategies to minimize the risk of nausea in vulnerable individuals are discussed.

Administration of alcohol to alcohol-dependent individuals for research purposes, while contributing significantly to the fund of knowledge on etiology and treatment of alcohol dependence, has often raised clinical and ethical concerns that such exposure may adversely affect the individual's motivation to reduce drinking or abstain from drinking. In an attempt to evaluate these concerns, we conducted a naturalistic follow-up of subsequent drinking among individuals who participated in an alcohol self-administration study and also received a brief motivational intervention. Twenty-one non-treatment–seeking alcoholics participated in a study examining the effects of naltrexone on alcohol self-administration. Assessment of drinking during the 3 months following the laboratory study indicated that participants had significantly reduced the total number of drinking days and the number of drinks consumed per occasion, as compared to baseline levels. The findings suggest that participation in alcohol administration research does not adversely influence the subsequent drinking of alcohol-dependent individuals. Further, when the alcohol administration research is conducted carefully, with specific attention to the clinical needs of the participants, the risks of adverse effects on participants' drinking behavior is minimal, and, in fact, there is scientific benefit to society and clinical benefit to the participants with regard to their alcoholism.

Sex differences exist in the reinforcing effects of nicotine, smoking cessation rates, and response to nicotine therapies. Sex differences in availability of nicotinic acetylcholine receptors containing the β(2) subunit (β(2)*-nAChRs) may underlie differential nicotine and tobacco smoking effects and related behaviors in women vs men.To examine β(2)*-nAChR availability in male and female smokers vs nonsmokers and to determine associations among β(2)*-nAChR availability, tobacco smoking characteristics, and female sex steroid hormone levels.Male (n = 26) and female (n = 28) tobacco smokers participated in an iodide 123-labeled 5-iodo-A-85380 ([(123)I]5-IA) single-photon emission computed tomography (SPECT) imaging session at 7 to 9 days of abstinence. Age-matched male (n = 26) and female (n = 30) nonsmokers participated in a [(123)I]5-IA SPECT imaging session. All participants completed a magnetic resonance imaging study.Academic imaging center.Tobacco smokers (n = 54) and age- and sex-matched nonsmokers (n = 56).The [(123)I]5-IA SPECT images were converted to equilibrium distribution volumes and were analyzed using regions of interest.The β(2)*-nAChR availability was significantly higher in male smokers compared with male nonsmokers in striatum, cortex, and cerebellum, but female smokers did not have higher β(2)*-nAChR availability than female nonsmokers in any region. In women, β(2)*-nAChR availability in the cortex and cerebellum was negatively and significantly correlated with progesterone level on the SPECT imaging day. In female smokers on imaging day, the progesterone level was positively and significantly correlated with depressive symptoms, craving for a cigarette, and nicotine withdrawal.The regulatory effects of nicotine in the brain (ie, tobacco smoking-induced upregulation of β(2)*-nAChRs) seem to be distinctly different between men and women, and female sex steroid hormones likely have a role in this regulation. These findings suggest an underlying neurochemical mechanism for the reported behavioral sex differences. To treat female smokers more effectively, it is critical that nonnicotinic-mediated medications should be explored.

The Internet represents a new and widely available forum for gambling. However, relatively few studies have examined Internet gambling in adolescents. This study sought to investigate the correlates of at-risk or problem gambling in adolescents acknowledging or denying gambling on the Internet.Survey data from 2,006 Connecticut high school student gamblers were analyzed using χ(2) and logistic regression analyses.At-risk/problem gambling was found more frequently in adolescent Internet gamblers than in non-Internet gamblers. Compared with at-risk/problem gambling in the non-Internet gambling group, at-risk/problem gambling in the Internet gambling group was more strongly associated with poor academic performance and substance use (particularly current heavy alcohol use; odds ratio 2.99; p = .03) and less strongly associated with gambling with friends (odds ratio 0.32; p = .0003). At-risk/problem gambling in the Internet and non-Internet gambling groups, respectively, was associated at p.05, each with multiple adverse measurements including dysphoria/depression (odds ratios 1.76 and 1.96), getting into serious fights (odds ratios 2.50 and 1.93), carrying weapons (odds ratios 2.11 and 1.90), and use of tobacco (odds ratios 2.05 and 1.88 for regular use), marijuana (odds ratios 2.02 and 1.39), and other drugs (odds ratios 3.24 and 1.67).Clinically, it is important to assess for teenagers' involvement in Internet gambling, particularly because adolescent at-risk/problem Internet gambling appears specifically associated with non-peer involvement, heavy alcohol use, and poor academic functioning.

The opiate antagonist naltrexone has demonstrated efficacy in the treatment of alcohol dependence and as a component of treatment to reduce heavy drinking. At present, there are no published dose-ranging clinical trials of the oral preparation for treatment of problem drinking. The present study evaluated the effects of naltrexone on alcohol use among the subset of hazardous drinkers (N = 102) who participated in a placebo-controlled, dose-ranging trial of oral naltrexone (25 mg, 50 mg and 100 mg doses) combined with open-label transdermal nicotine patch for enhancing smoking cessation. On the primary outcome—no hazardous drinking (drinking that exceeded weekly or daily limits) during treatment—25 mg and 50 mg naltrexone were superior to placebo (each p < 0.05). These findings remained after controlling for baseline predictors or smoking abstinence during treatment. Time to remission of hazardous drinking was examined as a secondary outcome with definitions of hazardous drinking based on weekly limits, daily limits and the combination of weekly and daily limits and the results were consistent with the primary findings. In conclusion, the findings suggest that naltrexone can reduce the risk of hazardous drinking in smokers who are not seeking or receiving alcohol treatment, providing strong evidence for the pharmacological effects of naltrexone on drinking. This effect appears to favor lower doses that may be better tolerated and less expensive than the higher 100 mg dose. Given its efficacy and favorable side effect profile, the 25 mg dose should be considered for future studies of combination therapy.

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence predicts relapse Ann M. Rasmusson , Ran Wu , Prashni Paliwal , George M. Anderson , Suchitra Krishnan-Sarin c a Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA b VA National Center for PTSD, Clinical Neuroscience Division, West Haven, CT, USA c Department of Psychiatry and Transdiscipliniary Tobacco Use Research Center, Yale University School of Medicine, New Haven, CT, USA d Department of Psychiatry and Division of Women’s BehavioralHealth, YaleUniversity School ofMedicine, NewHaven, CT, USA e Child Study Center, Department of Laboratory Medicine and Transdisciplinary Tobacco Use Research Center, Yale University School of Medicine, New Haven, CT, USA E-mail address: ann.rasmusson@yale.edu (A.M.Rasmusson)

Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose.Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers.We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence.The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers.

Background This study used an opioid antagonist challenge procedure to evaluate the responsivity of the endogenous opioid system in nicotine-dependent individuals, as evidenced by naloxone-induced alterations in both behavioral (withdrawal, craving) and neuroendocrine (cortisol levels) parameters. Methods Twenty subjects (9 smokers and 11 nonsmokers) participated in 4 laboratory sessions during which they were challenged with 0, 0.8, 1.6, or 3.2 mg/70 kg of naloxone and then monitored for 1 hour for subjective signs and symptoms of opiate-like withdrawal, nicotine craving, and alterations in cortisol levels. Results Nicotine-dependent subjects evidenced naloxone dose-dependent increases in withdrawal signs and symptoms. Lower doses of naloxone also produced increases in urges to smoke (craving) and tiredness in smokers. Smokers, when compared with nonsmokers, had lower prenaloxone baseline levels of cortisol and attenuated cortisol release in response to challenge with naloxone. Conclusion These results provide preliminary evidence to suggest that long-term exposure to cigarette smoke is associated with alterations in the responsivity of the endogenous opioid system and the hypothalamic-pituitary-adrenal axis that may contribute to the development of nicotine dependence.

Introduction Smoking and gambling are two significant public health concerns. Little is known about the association of smoking and gambling in adolescents. The current study of high-school adolescents examined: (1) smoking behavior by problem-gambling severity and (2) health-related variables by problem-gambling severity and smoking status. Methods Analyses utilized survey data from 1591 Connecticut high-school students. Adolescents were classified by problem-gambling severity (Low-Risk Gambling [LRG], At-Risk/Problem Gambling [ARPG]) and smoking status (current smoker, non-smoker). Analyses examined the smoking behavior of ARPG versus LRG adolescents as well as the smoking-by-problem-gambling-severity interactions for health and well-being measures (e.g., grades, substance use). Chi-square and logistic regression analyses were used; the latter controlled for gender, race/ethnicity, school grade, and family structure. Results More adolescents with ARPG than LRG reported regular smoking, heavy smoking, early smoking onset, no smoking quit attempts, and parental approval of smoking. ARPG and LRG adolescents who smoked were more likely to report poor grades, lifetime use of marijuana and other drugs, current heavy alcohol use, current caffeine use, depression, and aggressive behaviors and less likely to report participation in extracurricular activities. The association between not participating in extracurricular activities and smoking was statistically stronger in the LRG compared to the ARPG groups. Post-hoc analyses implicated a range of extracurricular activities including team sports, school clubs, and church activities. Conclusions Smoking was associated with poorer health-related behaviors in both ARPG and LRG groups. Interventions with adolescents may benefit from targeting both smoking and gambling., Highlights • We examined adolescent health behaviors by smoking status and gambling severity. • Smoking was associated with poorer health behaviors for adolescent gamblers. • Considering smoking may be helpful in interventions with adolescent gamblers.