Effects of a digital cognitive behavioral therapy for insomnia on sleep and alcohol consumption in heavy drinkers: A randomized pilot study.

BACKGROUND: Insomnia is a well-established, prospective risk factor for Alcohol Use Disorder. Thus, targeting sleep problems could serve as a novel and efficacious means of reducing problematic drinking. Here, we examined the potential utility of a well-validated, interactive, easy to use, self-paced digital cognitive behavioral therapy for insomnia program. In a randomized, single-blind pilot study, we examined the impact of treatment with Sleep Healthy Using the Internet (SHUTi) on drinking and sleep outcomes in a sample of heavy drinkers with insomnia. METHODS: Heavy drinking men (n = 28) and women (n = 42) with insomnia were randomly assigned to complete either the SHUTi program or a control patient education program. Subjective measures of sleep and alcohol use were administered at baseline, immediately following completion of the intervention, 3 months post-intervention, and 6 months post-intervention. Sleep outcomes were assessed using the Insomnia Severity Index and Pittsburgh Sleep Quality Index. Drinking outcomes were assessed using the 30-Day Timeline Follow-Back calendar. We used linear mixed effects models to compare groups on both insomnia and drinking outcomes. RESULTS: Data from all 70 subjects (SHUTI: n = 40; control: n = 30) were analyzed. Linear mixed effects models showed that SHUTi significantly reduced insomnia symptoms (p = 0.01) and drinking outcomes (ps < 0.05) more than the control condition over time. Trend-level effects on sleep quality (p = 0.06) were also observed. No adverse events were reported. CONCLUSIONS: Improving sleep may be an effective treatment intervention for reducing hazardous drinking in at-risk individuals. Further, findings provide preliminary support for the implementation of an easily accessible health behavior intervention with significant public health impact in a high-risk population.

Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives.

Alcohol use is highly prevalent in young adult women and rates of alcohol use disorder are rising rapidly in this population. Further, emerging evidence suggests that circulating levels of ovarian hormones influence alcohol consumption, with increased consumption associated with higher estradiol and lower progesterone levels. However, less is known about the influence of synthetic hormones (contained in oral contraceptive (OC) pills) on alcohol use. The current study examined the influence of OC pill phase, ethinyl estradiol (EE) levels, and progestin levels on self-reported alcohol consumption in healthy female drinkers. Young adult female drinkers using OCs (N = 21) reported alcohol use across one OC pill pack using the Timeline Followback and provided blood samples during both pill phases to measure synthetic hormone levels. We compared alcohol use between OC pill phases (active vs. inactive) using linear mixed effects models for repeated measures and examined correlations between alcohol use and EE and progestin levels. Results showed that women with higher EE levels reported increased alcohol consumption (r = 0.56, p = 0.01) and binge drinking (r = 0.45, p = 0.04) in the active pill phase. Progestin levels and pill phase were not significantly associated with alcohol consumption. These findings provide preliminary data suggesting increased levels of EE from OC pills are associated with excessive alcohol consumption in women. Further research is needed to determine if EE plays a causal role in increased alcohol consumption. This line of research could inform female-specific AUD prevention and treatment strategies among the large subpopulation of women using hormonal contraceptives.

Synthetic contraceptive hormones occlude the ability of nicotine to reduce ethanol consumption in ovary-intact female rats.

Rates of tobacco and alcohol use in women are rising, and women are more vulnerable than men to escalating tobacco and alcohol use. Many women use hormonal birth control, with the oral contraceptive pill being the most prevalent. Oral contraceptives contain both a progestin (synthetic progesterone) and a synthetic estrogen (ethinyl estradiol; EE) and are contraindicated for women over 35 years who smoke. Despite this, no studies have examined how synthetic contraceptive hormones impact this pattern of polysubstance use in females. To address this critical gap in the field, we treated ovary-intact female rats with either sesame oil (vehicle), the progestin levonorgestrel (LEVO; contained in formulations such as Alesse®), or the combination of EE+LEVO in addition to either undergoing single (nicotine or saline) or polydrug (nicotine and ethanol; EtOH) self-administration (SA) in a sequential use model. Rats preferred EtOH over water following extended EtOH drinking experience as well as after nicotine or saline SA experience, and rats undergoing only nicotine SA (water controls) consumed more nicotine as compared to rats co-using EtOH and nicotine. Importantly, this effect was occluded in groups treated with contraceptive hormones. In the sequential use group, both LEVO alone and the EE+LEVO combination occluded the ability of nicotine to decrease EtOH consumption. Interestingly, demand experiments suggest an economic substitute effect between nicotine and EtOH. Together, we show that chronic synthetic hormone exposure impacts nicotine and EtOH sequential use, demonstrating the crucial need to understand how chronic use of different contraceptive formulations alter patterns of polydrug use in women.

The importance of translationally evaluating steroid hormone contributions to substance use.

Clinically, women appear to be more susceptible to certain aspects of substance use disorders (SUDs). The steroid hormones 17ß-estradiol (E2) and progesterone (Pg) have been linked to women-specific drug behaviors. Here, we review clinical and preclinical studies investigating how cycling ovarian hormones affect nicotine-, cocaine-, and opioid-related behaviors. We also highlight gaps in the literature regarding how synthetic steroid hormone use may influence drug-related behaviors. In addition, we explore how E2 and Pg are known to interact in brain reward pathways and provide evidence of how these interactions may influence drug-related behaviors. The synthesis of this review demonstrates the critical need to study women-specific factors that may influence aspects of SUDs, which may play important roles in addiction processes in a sex-specific fashion. It is important to understand factors that impact women's health and may be key to moving the field forward toward more efficacious and individualized treatment strategies.

Heightened motor impairment as a protective factor against heavy drinking in individuals with high alcohol-induced disinhibition.

BACKGROUND: Behavioral disinhibition and motor impairment are both acutely elevated following alcohol consumption, and individual differences in sensitivity to alcohol-induced increases in these effects are associated with drinking habits. Specifically, high alcohol-induced disinhibition and low motor impairment have been identified as separate markers for alcohol-related problems. This study tested the degree to which alcohol-induced disinhibition and motor impairment jointly predict heavy drinking. We hypothesized that heavier drinkers would exhibit a combination of high sensitivity to alcohol-induced disinhibition and low sensitivity to its motor impairing effect. METHODS: Data from three studies were aggregated to comprise a sample of 96 young adults. Participants' motor coordination (grooved pegboard) and behavioral disinhibition (cued go/no-go) were assessed following consumption of 0.65 g/kg alcohol and a placebo during separate sessions. RESULTS: As BAC was ascending, alcohol increased motor impairment and disinhibition compared to placebo. Combined effects at this time of alcohol on motor impairment and disinhibition predicted typical drinking habits. Specifically, a combination of high sensitivity to alcohol's disinhibiting effect and low sensitivity to its motor impairing effect was associated with heavy drinking. As BAC was descending, only reduced sensitivity to motor impairment remained as a predictor of heavy drinking. CONCLUSIONS: The findings suggest that although motor impairment following alcohol consumption is associated with certain negative outcomes (e.g., increased risk for physical injury and motor vehicle accidents), such heightened motor impairment from alcohol may actually serve as a protective factor against the excessive drinking that can accompany the disinhibiting effect of alcohol.

Translational findings linking poor inhibitory control and heightened drug reward sensitivity.

Poor inhibitory control and heightened sensitivity to drug reward are two well-established risk factors for substance use disorders. Although these risk factors have traditionally been studied independently, there is reason to expect they may be related at the neurobiological level. Here, translational studies investigating the association between poor inhibition and greater drug reward sensitivity in both laboratory animals and humans are reviewed. Findings show that in animals, inhibitory deficits are associated with greater self-administration of cocaine, nicotine, 3,4-methylenedioxy-methamphetamine (MDMA), and alcohol, but not heroin. Likewise, in healthy human volunteers, poor inhibitory control and less brain engagement in right frontal regions during inhibition are associated with greater and more positive subjective responses to amphetamine and alcohol. The potential neurobiological mechanisms underlying this association are discussed, including the number or function of striatal dopamine D2 receptors, as well as the implications of the findings and directions for future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

"Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences": Clarification.

Reports a clarification to "Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences" by Holley C. Allen, Michael J. Wesley, Jessica Weafer and Mark T. Fillmore (Psychology of Addictive Behaviors, Advanced Online Publication, May 05, 2022, np). In the original article, simultaneous linear regression analyses examined the role of sex and trait impulsivity differences in participants' unintoxicated level of behavioral impulsivity and sensitivity to alcohol-induced increases in disinhibition. High levels of trait impulsivity were associated with higher unintoxicated disinhibition; however, no sex difference in this relationship was obtained. Similarly, high attention impulsivity was associated with elevated unintoxicated disinhibition, but no sex difference in this relationship was obtained. It is likely that the inclusion of participants with ADHD in the original analyses disproportionately accounted for the sex differences initially obtained. This reanalysis suggests that behavioral disinhibition serves as a broad indicator of trait impulsivity in both men and women. (The following abstract of the original article appeared in record 2022-58551-001). OBJECTIVE: Higher trait impulsivity is associated with more impulsive responding on certain behavioral measures of disinhibition. Additionally, behavioral disinhibition is acutely elevated following alcohol consumption. The present study examined the possibility that trait impulsivity may predict individual differences in sensitivity to the disinhibiting effect of alcohol. Specifically, the present study tested the hypothesis that those with elevated trait impulsivity also experience heightened sensitivity to the disinhibiting effect of alcohol, which might further compound their tendency toward impulsive action. METHOD: To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. RESULTS: Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. CONCLUSIONS: These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sex Differences in the Association Between Poor Sleep Quality and Alcohol-Related Problems Among Heavy Drinkers With Insomnia.

Background: Alcohol Use Disorder (AUD) and insomnia are highly comorbid; at least 40% of individuals with AUD suffer from insomnia. Women are more likely to report insomnia than men and have seen a concerning rise in rates of AUD in recent years. As such, the association between AUD and insomnia could be particularly pronounced in women. However, currently little is known regarding sex differences in this association. Here we examined the degree to which relationships between alcohol use and sleep quality differ between women and men. Methods: Heavy drinking women (n = 66) and men (n = 45) completed the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Alcohol Use Disorders Identification Test (AUDIT) to assess alcohol use and alcohol-related problems. Hierarchical regression analyses were conducted to determine sex differences in the association between poor sleep quality and alcohol-related problems. Results: After controlling for age, global subjective stress, and depression, sex significantly moderated the positive association between poor sleep quality and alcohol-related problems. Further analyses of the simple slopes for each sex revealed that poorer sleep quality (i.e., higher scores on the PSQI) were associated with greater alcohol-related problems (i.e., higher scores on the AUDIT) in women, but not in men. Conclusion: These results suggest that in heavy drinkers with insomnia, poor sleep is more strongly associated with drinking problems in women than in men. Future research is needed to investigate potential mechanisms underlying this relationship. Specifically, it will be important to determine whether sleep problems in heavy drinking women are a cause or consequence, or both, of heavy drinking.

Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences.

[Clarification Notice: A clarification for this article was reported online in Psychology of Addictive Behaviors on Aug 18 2022 (see record 2022-92429-001). In the original article, simultaneous linear regression analyses examined the role of sex and trait impulsivity differences in participants' unintoxicated level of behavioral impulsivity and sensitivity to alcohol-induced increases in disinhibition. High levels of trait impulsivity were associated with higher unintoxicated disinhibition; however, no sex difference in this relationship was obtained. Similarly, high attention impulsivity was associated with elevated unintoxicated disinhibition, but no sex difference in this relationship was obtained. It is likely that the inclusion of participants with ADHD in the original analyses disproportionately accounted for the sex differences initially obtained. This reanalysis suggests that behavioral disinhibition serves as a broad indicator of trait impulsivity in both men and women.] Objective: Higher trait impulsivity is associated with more impulsive responding on certain behavioral measures of disinhibition. Additionally, behavioral disinhibition is acutely elevated following alcohol consumption. The present study examined the possibility that trait impulsivity may predict individual differences in sensitivity to the disinhibiting effect of alcohol. Specifically, the present study tested the hypothesis that those with elevated trait impulsivity also experience heightened sensitivity to the disinhibiting effect of alcohol, which might further compound their tendency toward impulsive action. METHOD: To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. RESULTS: Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. CONCLUSIONS: These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Alcohol use, sleep, and depression among family caregivers in the time of COVID-19.

The COVID-19 pandemic has substantially altered daily life around the world, resulting in significant impacts on health behaviors. The additional burdens imposed by family caregiving (i.e., providing unpaid care for children and/or adults) may further exacerbate negative effects of the pandemic on health and health behaviors, including increased alcohol consumption, poor sleep, and increased depressive symptoms. The current study examined this possibility. Participants (N = 320, mean age = 35.11 years) completed an online questionnaire assessing alcohol use, sleep, and depression during the COVID-19 pandemic (June-August 2020) and retrospectively assessed the same health behaviors in the months prior to the pandemic. Insomnia severity increased, sleep quality decreased, and depressive symptoms increased for both caregivers and non-caregivers during the pandemic (p < 0.001). By contrast, alcohol consumption increased among caregivers only (p < 0.05). Further, increased alcohol use was associated with decreased sleep quality and increased insomnia symptoms among caregivers, but not non-caregivers. While additional longitudinal research is warranted in this population, our findings offer important insight on self-reported changes in alcohol consumption, sleep patterns, and mood among family caregivers during the COVID-19 pandemic.

Human behavioral pharmacology of stimulant drugs: An update and narrative review.

Stimulant use disorders present an enduring public health concern. Chronic stimulant use is associated with a range of health problems, with notable increases in stimulant overdose that disproportionately affect marginalized populations. With these persistent problems, it is important to understand the behavioral and pharmacological factors that contribute to stimulant use in humans. The purpose of this chapter is to provide an update and narrative review on recent human laboratory research that has evaluated the behavioral pharmacology of stimulant drugs. We focus on two prototypic stimulants: cocaine as a prototype monoamine reuptake inhibitor and d-amphetamine as a prototype monoamine releaser. As such, placebo controlled human laboratory studies that involved administration of doses of cocaine or d-amphetamine and were published in peer reviewed journals within the last 10 years (i.e., since 2011) are reviewed. Primary outcomes from these studies are subjective effects, reinforcing effects, cognitive/behavioral effects, and discriminative stimulus effects. Both cocaine and d-amphetamine produce classical stimulant-like behavioral effects (e.g., increase positive subjective effects, function as reinforcers), but there are notable gaps in the literature including understanding sex differences in response to stimulant drugs, cognitive-behavioral effects of stimulants, and influence of use history (e.g., relatively drug naïve vs drug experienced) on stimulant effects.

Effects of Methamphetamine on Within- and Between-Network Connectivity in Healthy Adults.

Methamphetamine (MA) abuse remains an urgent public health problem. Understanding how the drug affects brain function will help to identify how it leads to abuse and dependence. Previous studies indicate that MA and other stimulants have complex effects on resting state functional connectivity. Here, we used a hypothesis-free approach to examine the acute effects of MA (20 mg oral) versus placebo on neural connectivity in healthy adults. Using networks identified by an independent component analysis with placebo data, we examined the effects of MA on connectivity within and between resting state networks. The drug did not significantly alter connectivity within networks. MA did alter connectivity between some networks: it increased connectivity between both the thalamus and cerebellum to sensorimotor and middle temporal gyrus. However, MA decreased connectivity between sensorimotor and middle temporal gyrus networks. MA produced its expected subjective effects, but these were not significantly related to connectivity. The findings extend our knowledge of how MA affects connectivity, by reporting that it affects between-network connectivity but not within-network connectivity. Future studies with other behavioral measures may reveal relationships between the neural and behavioral actions of the drug.

Neural correlates of inhibitory control are associated with stimulant-like effects of alcohol.

Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to which neural activity during inhibition was associated with subjective reports of stimulation following alcohol. To assess neural changes during inhibition, moderate alcohol drinkers performed a stop signal task during fMRI without drug. To assess subjective responses to alcohol they ingested alcohol (0.8 g/kg) or placebo beverages under double-blind conditions and provided subjective reports of stimulation and sedation. Feelings of stimulation following alcohol were inversely associated with activity in the supplementary motor area, insula, and middle frontal gyrus during inhibition (successful stop trials compared to go trials). Feelings of sedation did not correlate with brain activation. These results extend previous findings suggesting that poor inhibitory control is associated with more positive subjective responses to alcohol. These interrelated risk factors may contribute to susceptibility to future excessive alcohol use, and ultimately lead to neurobiological targets to prevent or treat AUD.

Subjective responses predict d-amphetamine choice in healthy volunteers.

BACKGROUND: It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However, recreational drug use sometimes occurs in the absence of positive subjective effects, suggesting that other factors contribute. Here, we examine the extent to which the direct subjective effects of amphetamine, a commonly misused stimulant, predict subsequent choice of the drug vs placebo. METHODS: Healthy adults (N = 112) participated in a five-session amphetamine choice study. On the first four sessions, participants sampled either 20 mg d-amphetamine or placebo in color-coded capsules two times each. On the fifth session, they chose which color (d-amphetamine or placebo) they preferred. We examined the choice of drug vs placebo in relation to demographic characteristics, baseline mood states, personality and subjective and cardiovascular responses to acute administration of the drug. RESULTS: Eighty-one participants chose amphetamine (Choosers) while 31 chose placebo (Non-choosers). Overall, amphetamine produced typical stimulant-like effects on subjective questionnaires, and it elevated heart rate and blood pressure vs placebo. Choosers reported greater positive mood, elation and stimulant-like effects following amphetamine compared to Non-choosers. The Choosers also exhibited a greater increase in systolic blood pressure, but not heart rate. The groups did not differ on demographic characteristics, mood states before drug administration or personality. CONCLUSIONS: These findings support the idea that pleasurable subjective responses to amphetamine, including positive mood, elation, and stimulant-like effects influence behavioral choice of the drug.

Striatal activation to monetary reward is associated with alcohol reward sensitivity.

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested the hypothesis that subjective response to acute rewarding effects of alcohol would be related to neural activation during monetary reward receipt relative to loss (in the absence of alcohol). Community-recruited healthy young social drinkers (N = 58) completed four laboratory sessions in which they received alcohol (0.8 g/kg) and placebo in alternating order under double-blind conditions, providing self-report measures of subjective response to alcohol at regular intervals. At a separate visit 1-3 weeks later, they completed a reward-guessing game, the 'Doors' task, during fMRI in a drug-free state. Participants who reported greater motivation (i.e., wanting) to consume more alcohol after a single moderate dose of alcohol also exhibited greater neural activation in the bilateral ventral caudate and the nucleus accumbens during reward receipt relative to loss. Striatal activation was not related to other subjective ratings including alcohol-induced sedation, stimulation, or pleasure (i.e., feeling, liking). Our study is the first to show that measures of alcohol reward are related to neural indices of monetary reward in humans. These results support growing evidence that individual differences in responses to drug and nondrug reward are linked and together form a risk profile for drug use or abuse, particularly in young adults.

Neural activation during anticipation of monetary gain or loss does not associate with positive subjective response to alcohol in binge drinkers.

BACKGROUND: Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation, liking or wanting more after a dose of alcohol and neural-based responses to anticipation of monetary gain and loss. METHODS: Young adult binge drinkers (N = 56) aged 21-29, with no history of Substance Use Disorder completed five experimental sessions. These included four laboratory sessions in which they rated their subjective responses to alcohol (0.8 g/kg for men, 0.68 g/kg for women) or placebo, and a single functional magnetic resonance imaging session in which they completed a monetary incentive delay task. During the scan, we recorded neural signal related to anticipation of winning $5 or $1.50 compared to winning no money (WinMoney-WinZero), losing $5 or $1.50 compared to losing no money (LoseMoney-LoseZero), and winning $5 or $1.50 compared to losing $5 or $1.50 (WinMoney-LoseMoney), in reward related regions. RESULTS: There were no significant associations between subjective ratings of "Feel Drug Effect", "Like Drug Effect", "Want More", stimulation or sedation following the acute alcohol challenge and neural activation in reward related regions during anticipation of monetary gain or loss. CONCLUSIONS: These results suggest that sensitivity of neural reward circuits is not directly related to rewarding subjective experiences from alcohol. Taken together with previous studies, the present findings indicate that the association between the subjective effects of drugs and reward-related brain activity depends on the drugs, tasks or subject samples under study.

Acute rewarding and disinhibiting effects of alcohol as indicators of drinking habits.

RATIONALE: Laboratory studies have reliably shown that heightened sensitivity to the rewarding effects of alcohol is associated with heavier drinking patterns. More recently, there has been research to suggest that heightened sensitivity to the disinhibiting effects of alcohol might also contribute to drinking habits. Most research on the acute effects of alcohol has focused on drinking magnitudes averaged across participants with little attention paid to how individual differences influence alcohol abuse potential. In large part, this is due to limited sample sizes in previous laboratory studies. OBJECTIVES: This study overcomes previous limitations by testing the degree to which individual differences in acute sensitivity and tolerance to the rewarding and disinhibiting effects of alcohol relate to drinking behavior in a large sample size. METHODS: Data from six laboratory studies were aggregated to comprise a sample of 181 adults. Participants' level of "liking" (the effects of alcohol) and disinhibition were assessed following 0.65 g/kg alcohol once during the ascending limb of the blood alcohol concentration (BAC) curve and again at the same BAC during the descending limb of the curve. The measures were also assessed following placebo. RESULTS: Alcohol increased ratings of liking and behavioral disinhibition. Heavier drinking was associated with heightened sensitivity to liking on the ascending limb. Additionally, those who showed reduced acute tolerance to both disinhibition and liking were also heavier drinkers. CONCLUSIONS: These data suggest that individual variability in liking the effects of alcohol and persistent disinhibition are key indicators of drinking habits.

Subjective Effects of Alcohol Predict Alcohol Choice in Social Drinkers.

INTRODUCTION: Alcohol is among the most commonly used psychoactive drugs, yet it can produce markedly different subjective effects in different people. Certain effects, including both heightened stimulatory effects and lesser sedative effects, are thought to predict repeated or excessive use. However, we do not fully understand the nature of these individual differences or their relationships to alcohol consumption. This controlled laboratory study examined subjective and physiologic responses to a moderate dose of alcohol in social drinkers in relation to the subjects' decision to consume alcohol. METHODS: Healthy adult volunteers (N = 95) participated in a 5-session double-blind alcohol choice study. On the first 4 sessions, they received alcohol (0.8 g/kg) and placebo in alternating order, and on the fifth session, they chose and consumed whichever of the 2 they preferred. During each session, participants completed the Profile of Mood States (POMS) and Biphasic Alcohol Effects Scale (BAES) questionnaires and had their vitals recorded every 30 minutes. We compared subjective and physiologic response to alcohol during the sampling sessions in participants who chose alcohol or placebo on session 5. RESULTS: Of the 95 participants, 55 chose alcohol (choosers) and 40 chose placebo (nonchoosers). In the full sample, alcohol produced its expected effects (e.g., increased friendliness, elation, and vigor (POMS), and stimulation and sedation (BAES)). The chooser and nonchooser groups did not differ in demographic characteristics, blood alcohol levels, or cardiovascular measures. However, the choosers experienced greater alcohol-induced increases in positive mood (POMS) and liked the drug more, whereas the nonchoosers experienced greater anger, anxiety (POMS), and sedation (BAES) after alcohol. CONCLUSION: Both greater positive mood effects and lesser sedative effects after alcohol predicted preference under controlled conditions, suggesting that both factors can predict future consumption of alcohol.

Stability of acute responses to drugs in humans across repeated testing: Findings with alcohol and amphetamine.

BACKGROUND: Controlled drug challenge studies provide valuable information about the acute behavioral effects of drugs, including individual differences that may affect risk for abuse. One question that arises in such studies is whether a single administration of a drug (and placebo) provides an accurate measure of response to the drug. METHODS: Here, we examined data from two studies, one with alcohol and one with amphetamine, in which participants received two administrations of the drug and placebo. In this analysis we assess the stability of acute subjective and cardiovascular responses to the drugs across the two administrations. We examine i) systematic increases or decreases to the drugs from the first to the second administration, ii) test-retest reliability within individuals and iii) the accuracy of the acute drug responses to predict drug choice in a later session. RESULTS: Responses were largely stable across sessions, although on the second session amphetamine "liking" was higher, and subjective responses to placebo including "liking" and "want more" decreased in both studies. Test-retest reliability within individuals was high. Responses during the first drug administration were as accurate in predicting drug choice as responses during both administrations combined. CONCLUSIONS: Our findings indicate that a single administration of drug (and placebo) provides a good index of an individual's responses to alcohol or amphetamine, when participants are tested under controlled experimental conditions.

Sex Differences in Neural Correlates of Inhibitory Control.

This chapter reviews the current evidence for sex differences in neural function underlying inhibitory control. Specifically, the chapter focuses on sex differences in functional magnetic resonance imaging (fMRI) measures of brain engagement during response inhibition on stop signal and go/no-go tasks. Sex differences appear to exist in these measures, but the direction of effect depends on the population studied, the task used, and whether successful or unsuccessful inhibition is examined. For successful inhibition, healthy men typically show greater brain engagement in right frontal regions typically implicated in inhibitory control (e.g., inferior frontal gyrus and supplementary motor area) than women, especially when performing the stop signal task. However, in younger populations or when controlling for the effects of age, women tend to show greater brain engagement than men, especially when performing the go/no-go task. For unsuccessful inhibition, women tend to show greater brain engagement compared to men in the anterior cingulate cortex and thalamus. Taken together, findings suggest that sex differences in neural responses to response inhibition depend on the specific type of inhibition studied and on whether the inhibition is successful or unsuccessful. Men exhibit greater response during successful inhibition, whereas women consistently display greater neural responses during unsuccessful inhibition. The chapter highlights limitations and gaps in this research to date, including a lack of consideration of the role of sex hormones and menstrual cycle phase, and suggests future directions for this line of research.