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Experimental and Clinical Psychopharmacology - Vol 22, Iss 5

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Experimental & Clinical Psychopharmacology Experimental and Clinical Psychopharmacology seeks to promote the discipline of psychopharmacology in its fullest diversity. Psychopharmacology necessarily involves behavioral change, psychological processes, or their physiological substrates as one central variable and psychopharmacological agents as a second central variable. Such agents will include drugs, medications, and chemicals encountered in the workplace or environment.
Copyright 2014 American Psychological Association
  • Consideration of sex in clinical trials of transdermal nicotine patch: A systematic review.
    Transdermal nicotine patch (TNP) is 1 of the most commonly used smoking cessation treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of the current review was to synthesize how sex has been considered in published clinical trials of TNP for smoking cessation. The specific aims of the study were to examine the inclusion of sex in analyses of cessation outcomes, TNP-related variables (compliance, side effects), and quit-related variables (withdrawal, cravings); to review the consideration of sex-related variables (menstrual cycle phase, pregnancy); and to identify needs for future research. Potential articles published through December 31, 2013 were identified through a MEDLINE search of the terms “clinical trial,” “nicotine patch,” and “smoking cessation.” Forty-two studies used all 3 terms and met the inclusion criteria. Approximately half of the studies reported that they considered sex in smoking cessation outcomes, with 15 studies finding no difference by sex and 7 studies finding better outcomes for men versus women. Only 5 studies reported data on outcomes by sex in their publications. No studies reported analysis of TNP compliance or withdrawal by sex. In the 1 study that examined side effects by sex, more women than men reported discontinuing TNP because of skin irritation. No study examined the association of cessation outcomes with menstrual cycle phase. There is a need to include sex in research on TNP, as well as other pharmacological and behavioral smoking treatments, to clarify the picture of treatment efficacy for women compared with men. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Examining educational attainment, prepregnancy smoking rate, and delay discounting as predictors of spontaneous quitting among pregnant smokers.
    We investigated three potential predictors (educational attainment, prepregnancy smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant smokers. These predictors were examined alone and in combination with other potential predictors using study-intake assessments from controlled clinical trials examining the efficacy of financial incentives for smoking cessation and relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118 spontaneous quitters) recruited from the greater Burlington, VT, area contributed to this secondary analysis, including psychiatric/sociodemographic characteristics, smoking characteristics, and performance on a computerized DD task. Educational attainment, smoking rate, and DD values were each significant predictors of spontaneous quitting in univariate analyses. A model examining those three predictors together retained educational attainment as a main effect and revealed a significant interaction of DD and smoking rate (i.e., DD was a significant predictor at lower but not higher smoking rates). A final model considering all potential predictors, included education, the interaction of DD and smoking rate, and five additional predictors (i.e., stress ratings, the belief that smoking during pregnancy will “greatly harm my baby,” age of smoking initiation, marital status, and prior quit attempts during pregnancy). The study presented here contributes new knowledge on predictors of spontaneous quitting among pregnant smokers with substantive practical implications for reducing smoking during pregnancy. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Effects of sequential fluoxetine and gender on prequit depressive symptoms, affect, craving, and quit day abstinence in smokers with elevated depressive symptoms: A growth curve modeling approach.
    Although the important roles of postquit affect and withdrawal symptoms in the process of smoking cessation have been well established, little is known about the relations between prequit affective trajectories and cessation outcome on the target quit date (TQD). This study examined whether a 16-week course of fluoxetine initiated 8 weeks prequit (“sequential” fluoxetine) improved TQD abstinence relative to placebo through its effects on prequit depressive symptoms, affect (withdrawal-relevant negative affect, general negative affect, and positive affect), and craving to smoke among 206 smokers with elevated depressed symptoms. The moderating effects of gender were also examined. In total, 83 smokers (40%) failed to achieve abstinence on TQD, with no difference between treatment conditions or gender. Overall structural equation models showed that fluoxetine had significant indirect effects on TQD abstinence through changes in prequit withdrawal-relevant negative affect and craving, but not depressive symptoms. However, multigroup analyses revealed gender differences. Sequential fluoxetine reduced prequit depressive symptoms, withdrawal-relevant negative affect, and craving only among women. Reduction in prequit depressive symptoms and craving among women, and withdrawal-relevant negative affect among men was associated with TQD abstinence. Moreover, exploratory analysis showed negative trend-level indirect effects of fluoxetine on TQD abstinence via increased side effects, regardless of gender. This study demonstrated the importance of considering gender when examining treatment efficacy. Identifying ways to further reduce prequit depressive symptoms and craving for women and withdrawal-relevant negative affect for men whereas alleviating side effects may help smokers with elevated depressed symptoms achieve the first smoking cessation milestone. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink.
    This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Topiramate’s reduction of body mass index in heavy drinkers: Lack of moderation by a GRIK1 polymorphism.
    Topiramate, which interacts with multiple neurotransmitter and enzyme systems, is approved by the Food and Drug Administration to treat seizure disorder, prevent migraine, and (in combination with phentermine) reduce weight. Topiramate has also been shown in multiple studies to reduce heavy drinking. The authors found that topiramate 200 mg/day significantly reduced heavy drinking in heavy drinkers with a treatment goal of reduced drinking (Kranzler et al., 2014). Further, in the European American (EA) subsample (n = 122), a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes the GluK1 subunit of the kainate receptor, moderated the effect on heavy drinking days. Here the authors examined the effects of topiramate on body mass index (BMI) and the moderating effect of rs2832407 in the EA subsample from Kranzler et al. (2014). Across the 12 weeks of treatment, BMI was reduced by 1.2 kg/m2 (p <.001) in the topiramate group but was unchanged in the placebo group. There was no evidence of moderation by rs2832407 of topiramate’s effects on BMI. Controlling for changes in drinking and other potential confounders did not alter the findings. These results suggest that the effect of topiramate on drinking behavior, in which the GluK1-containing kainate receptor appears to play a key role, can be dissociated from its effect on weight, the specific mechanism of which remains to be determined. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • A naturalistic comparison of the effectiveness of methadone and two sublingual formulations of buprenorphine on maintenance treatment outcomes: Findings from a retrospective multisite study.
    Objective: This study sought to compare the effectiveness of the 3 most commonly prescribed maintenance medications in the United States indicated for the treatment of opioid dependence in reducing illicit drug use and retaining patients in treatment. Method: Data were abstracted from electronic medical records for 3,233 patients admitted to 34 maintenance treatment facilities located throughout the United States during the period of July 1, 2012, through July 1, 2013. Patients were grouped into 1 of 3 medication categories based on their selection at intake (methadone [n = 2,738; M dosage = 64.64 mg/d, SD = 25.58], Suboxone [n = 102; M dosage = 9.75 mg/d, SD = 4.04], or Subutex [n = 393; M dosage = 12.21 mg/d, SD = 5.31]) and were studied through retrospective chart review for 6 months or until treatment discharge. Two measures of patient retention in treatment and urinalysis drug screen (UDS) findings for both opioids and various nonopioid substances comprised the study outcomes. Results: The average length of stay (LOS) in terms of days in treatment for the methadone group (M = 169.86, SE = 5.02) was significantly longer than both the Subutex (M = 69.34, SE = 23.43) and Suboxone (M = 119.35, SE = 20.82) groups. The Suboxone group evinced a significantly longer average LOS relative to the Subutex group. After adjustment for relevant covariates, patients maintained on methadone were 3.73 times (95% confidence interval [CI]= 2.82–4.92) and 2.48 times (95% CI = 1.57–3.92) more likely to be retained in treatment at 6 months than patients prescribed Subutex and Suboxone, respectively. The 6-month prevalence rates of positive UDS findings for both opioids and nonopioid substances were similar across medication groups. Conclusions: Comparable rates of illicit drug use at 6 months may be expected irrespective of maintenance medication, while increased retention may be expected for patients maintained on methadone relative to those maintained on Suboxone or Subutex. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Predictive validity of delay discounting behavior in adolescence: A longitudinal twin study.
    A standard assumption in the delay discounting literature is that individuals who exhibit steeper discounting of hypothetical rewards also experience greater difficulty deferring gratification to real-world rewards. There is ample cross-sectional evidence that delay discounting paradigms reflect a variety of maladaptive psychosocial outcomes, including substance use pathology. We sought to determine whether a computerized assessment of hypothetical delay discounting (HDD) taps into behavioral impulsivity in a community sample of adolescent twins (N = 675). Using a longitudinal design, we hypothesized that greater HDD at age 14–15 predicts real-world impulsive choices and risk for substance use disorders in late adolescence. We also examined the genetic and environmental structure of HDD performance. Individual differences in HDD behavior showed moderate heritability, and were prospectively associated with real-world temporal discounting at age 17–18. Contrary to expectations, HDD was not consistently related to substance use or trait impulsivity. Although a significant association between HDD behavior and past substance use emerged in males, this effect was mediated by cognitive ability. In both sexes, HDD failed to predict a comprehensive index of substance use problems and behavioral disinhibition in late adolescence. In sum, we present some of the first evidence that HDD performance is heritable and predictive of real-world temporal discounting of rewards. Nevertheless, HDD might not serve as a valid marker of substance use disorder risk in younger adolescents, particularly females. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • A new look at risk-taking: Using a translational approach to examine risk-taking behavior on the balloon analogue risk task.
    Models of risk-taking typically assume that the variability of outcomes is important in the likelihood of making a risky choice. In an animal model of the Balloon Analogue Risk Task (BART), within-session variability, or the coefficient of variability (CV), was found to be a novel predictor of behavior (Jentsch et al., 2010). Human studies have not investigated how BART performance differs when using the CV versus a traditional BART measure (e.g., number of pumps). This study sought to determine whether the CV provides a unique and valuable alternative index of risk-taking on the BART, and to determine the relationship of the CV to self-reported alcohol consumption. Young adult heavy drinkers (n = 58, 72% male, mean age 21.53) completed an assessment of drinking patterns and a modified version of the BART. Multiple regression results indicated that CV is a unique predictor of total explosions and total money earned on the BART. Higher levels of variability were associated with fewer explosions but less money earned, whereas more pumps was associated with more explosions but more money. Higher CV was also associated with lower lifetime and past 3 months peak drinking quantity, higher levels of self-efficacy to control drinking, and lower levels of drinking acceptability (i.e., injunctive norms). Total pumps was associated with higher lifetime peak drinking, lower self-efficacy to control drinking, and higher levels drinking acceptability. Overall, the CV can provide an alternative method of assessing BART performance and the association of risk-taking with drinking patterns. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Low-dose nicotine self-administration is reduced in adult male rats naïve to high doses of nicotine: Implications for nicotine product standards.
    Product standards that greatly reduce the content of nicotine within cigarettes may result in improved public health. The study presented here used an animal model to investigate whether individuals who start smoking after implementation of regulation may be affected differently from current smokers who form the basis of most clinical studies. One group of adult male rats (n = 14/group) acquired nicotine self-administration at a high nicotine dose (60 μg/kg/infusion) before experiencing a reduction to one to three low doses of nicotine (3.75, 7.5, or 15 μg/kg/infusion) or vehicle. Their self-administration behavior at the low doses was compared with a group of adult male rats given the opportunity to acquire nicotine self-administration at one of the same low doses or vehicle (n = 7–14/group). Second, the self-administration behavior of the acquisition group of rats was compared with their own self-administration behavior after experience self-administering a high dose of nicotine. A cocktail of non-nicotine cigarette smoke constituents was included in the vehicle for all rats across all phases of the study. Rats with a history of self-administering a high dose of nicotine had a higher rate of self-administration across the low doses than rats with no history. In addition, the number of earned infusions increased after rats experienced self-administration of a higher dose of nicotine. These data show that low-dose nicotine self-administration is higher after a dose reduction than during acquisition. If a nicotine reduction policy were implemented, then this policy may be especially effective at reducing acquisition of smoking. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Effects of baclofen and naltrexone, alone and in combination, on the consumption of palatable food in male rats.
    Excess consumption of palatable food has been shown to affect reward-related brain regions, and pharmaceutical treatments for drug addiction may also be effective in treating overeating of such foods. The GABA-B agonist baclofen and opioid antagonist naltrexone have both been used to treat addiction, and have been shown to suppress intake of certain foods. The combination of these drugs has shown to be more effective in reducing alcohol consumption than either drug alone. The present study assessed the effects of naltrexone and baclofen, alone and in combination, on intake of foods comprised of various macronutrients. Male Sprague–Dawley rats were given 12-hr daily access to chow and a fat emulsion, sugar–fat emulsion, or a sugar solution for 21 days. Rats were then administered (intraperitoneal) baclofen–naltrexone combinations (0.1 mg/kg naltrexone and 1.0 mg/kg baclofen, 1.0 mg/kg naltrexone and 1.8 mg/kg baclofen), and naltrexone (0.1, 1.0 mg/kg) and baclofen (1.0, 1.8 mg/kg) alone. The high dose of the baclofen–naltrexone combination reduced palatable food intake in both the fat and sugar–fat groups compared with vehicle, without affecting chow consumption in these groups. Naltrexone showed little significant effects on intake of either palatable food or chow. Baclofen also reduced palatable food intake in the fat and fat–sugar groups, but differences were only noted between the low and high dose. The combination of baclofen and naltrexone may be a useful tool in selectively targeting the consumption of high-fat and sugar- and fat-rich foods. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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