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.

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.

To Infuse or Ingest in Human Laboratory Alcohol Research.

Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper was to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, "To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs." We review the methodological approaches of each and highlight strengths and weaknesses pertaining to different research questions. We summarize methodological considerations to aid researchers in choosing the most appropriate method for their inquiry, considering exposure variability, alcohol expectancy effects, safety, bandwidth, technical skills, documentation of alcohol exposure, experimental variety, ecological validity, and cost. Ingestion of alcohol remains a common and often a preferable, methodological practice in alcohol research. Nonetheless, the main problem with ingestion is that even the most careful calculation of dose and control of dosing procedures yields substantial and uncontrollable variability in the participants' brain exposures to alcohol. Infusion methodologies provide precise exposure control but are technically complex and may be limited in ecological validity. We suggest that alcohol ingestion research may not be the same thing as alcohol exposure research; investigators should be aware of the advantages and disadvantages that the choice between ingestion and infusion of alcohol invokes.

Methamphetamine acutely alters frontostriatal resting state functional connectivity in healthy young adults.

Chronic use of methamphetamine impairs frontostriatal structure and function, which may result in increased incentive-motivational responses to drug cues and decreased regulation of drug-seeking behavior. However, less is known regarding how the drug affects these circuits after acute administration. The current study examined the effects of a single dose of methamphetamine on resting state frontostriatal functional connectivity in healthy volunteers. Participants (n = 22, 12 female) completed two sessions in which they received methamphetamine (20 mg) and placebo before a resting state scan during functional magnetic resonance imaging. Participants also provided self-report measures of euphoria and stimulation at regular intervals. We conducted seed-based voxelwise functional connectivity analyses using three bilateral striatal seed regions: nucleus accumbens (NAcc), caudate, and putamen and compared connectivity following methamphetamine versus placebo administration. Additionally, we conducted correlational analyses to assess if drug-induced changes in functional connectivity were related to changes in subjective response. Methamphetamine increased NAcc functional connectivity with medial frontal regions (ie, orbitofrontal cortex, medial frontal gyrus, and superior frontal gyrus) and decreased NAcc functional connectivity with subgenual anterior cingulate cortex (ACC). Methamphetamine also increased functional connectivity between putamen and left inferior frontal gyrus (IFG), and individuals who displayed greater drug-induced increase in connectivity reported less euphoria and stimulation. These findings provide important information regarding the effects of methamphetamine on brain function in nonaddicted individuals. Further studies will reveal whether such effects contribute to the abuse potential of the drug and whether they are related to the frontostriatal impairments observed after chronic methamphetamine use.

Neural correlates of inhibition and reward are negatively associated.

Individuals with impulsive and addictive disorders, including drug addiction, binge eating/obesity, and problem gambling, exhibit both impaired control over behavior and heightened sensitivity to reward. However, it is not known whether such deviation in inhibitory and reward circuitry among clinical populations is a cause or consequence of the disorders. Recent evidence suggests that these constructs may be related at the neural level, and together, increase risk for engaging in maladaptive behaviors. The current study examined the degree to which brain function during inhibition relates to brain function during receipt of reward in healthy young adults who have not yet developed problem behaviors. Participants completed the stop signal task to assess inhibitory control and the doors task to assess reactivity to monetary reward (win vs loss) during functional magnetic resonance imaging (fMRI). Brain activation during response inhibition was negatively correlated with brain activation during reward. Specifically, less brain activation in right prefrontal regions during inhibition, including the right inferior frontal gyrus, middle frontal gyrus, and supplementary motor area, was associated with greater brain activation in left ventral striatum during receipt of monetary reward. Moreover, these associations were stronger in binge drinkers compared to non-binge drinkers. These findings suggest that the systems are related even before the onset of impulsive or addictive disorders. As such, it is possible that the association between inhibitory and reward circuitry may be a prospective marker of risk.

Preliminary Evidence for Disrupted Nucleus Accumbens Reactivity and Connectivity to Reward in Binge Drinkers.

AIMS: Dysfunctional brain reward circuitry, particularly in the nucleus accumbens (NAcc), has been proposed as a risk factor for alcohol use disorder (AUD). This risk factor may be evident in binge drinkers (BD), who are at high risk for developing AUD. We examined whole-brain and NAcc reactivity to reward in BD compared to non-binge drinkers (NBD), hypothesizing that groups would differ in their neural reactivity and connectivity. METHODS: Healthy BD (N = 27) and NBD (N = 23)-none meeting AUD criteria-completed a reward-guessing game, the 'Doors' task, during functional magnetic resonance imaging. We conducted an exploratory whole-brain search for group differences, but given our a priori hypotheses, we also extracted activation from the NAcc to examine reactivity during reward (Win > Loss) and functional connectivity (FC) to the prefrontal cortex. RESULTS: Compared to NBD, BD exhibited greater activation in both the right and left NAcc during reward relative to loss. Additionally, NBD drinkers exhibited positive FC between the NAcc and dorsal anterior cingulate (dACC) whereas the BD showed negative FC between these regions. Furthermore, less NAcc-dACC FC was related to more past month alcohol use. CONCLUSIONS: Our results provide preliminary evidence that BD exhibit greater NAcc activation during reward receipt relative to loss. This is consistent with the broader AUD literature and suggests aberrant neural reactivity may precede disorder onset. In addition, BD exhibited less NAcc-dACC FC, perhaps reflecting deficient regulation of activation to rewards compared to losses. This profile of reward brain circuitry could represent neural correlates of vulnerability for AUD. SHORT SUMMARY: Healthy binge drinkers, at risk for alcohol use disorder, exhibited greater nucleus accumbens activation during reward relative to loss. In addition, binge drinkers exhibited reduced connectivity between the nucleus accumbens and dorsal anterior cingulate, which was associated with more past month alcohol use.

Genetic influences on ADHD symptom dimensions: Examination of a priori candidates, gene-based tests, genome-wide variation, and SNP heritability.

Although the heritability of ADHD is estimated to be high, identifying specific genetic markers remains challenging. Most studies to date have examined the genetic basis of ADHD by employing dichotomous diagnostic phenotypes, but, as ADHD symptoms tend to be phenotypically dimensional, an alternative and potentially informative approach is to examine continuous indices of inattention and hyperactivity-impulsivity symptoms. The current study aimed to identify genetic effects on dimensionally-focused adult ADHD-related phenotypes in 990 individuals of European ancestry with intentionally low levels of substance misuse to avoid confounding. The study used four complementary approaches: (1) analysis of a priori candidate loci identified in prior meta-analytic work; (2) gene-based analysis; (3) hypothesis-free genome-wide association testing; and (4) single nucleotide polymorphism (SNP) heritability via genomic-relatedness-matrix restricted maximum likelihood analysis (GREML). The GREML analysis included a bivariate model to test whether the ADHD symptom dimensions index the same genetic liability. The results revealed significant differential associations between two a priori loci and ADHD phenotypes, rs6296 in HTR1B with inattention and rs3746544 in SNAP-25 with hyperactivity-impulsivity. No significant gene-based or genome-wide associations were detected, but SNP heritability revealed that a large portion of genetic variance was accounted for by common SNPs (44%, 55%, and 59% for inattention, hyperactivity-impulsivity, and total ADHD, respectively) and substantial shared genetic variance across inattention and hyperactivity-impulsivity (86%). These findings reveal both unique and common patterns of genetic influences across dimensional ADHD-related phenotypes. More broadly, these findings reveal the value in using multiple methods to understand the genetic etiology of ADHD.

Effect of Alcohol on Encoding and Consolidation of Memory for Alcohol-Related Images.

BACKGROUND: Drug and alcohol abusers develop strong memories for drug-related stimuli. Preclinical studies suggest that such memories are a result of drug actions on reward pathways, which facilitate learning about drug-related stimuli. However, few controlled studies have investigated how drugs affect memory for drug-related stimuli in humans. METHODS: The current study examined the direct effect of alcohol on memory for images of alcohol-related or neutral beverages. Participants received alcohol (0.8 g/kg) either before viewing visual images (encoding condition; n = 20) or immediately after viewing them (consolidation condition; n = 20). A third group received placebo both before and after viewing the images (control condition; n = 19). Memory retrieval was tested exactly 48 hours later, in a drug-free state. RESULTS: Alcohol impaired memory in the encoding condition and enhanced memory in the consolidation condition, but these effects did not differ for alcohol-related and neutral beverage stimuli. However, in the encoding condition, participants who experienced greater alcohol-induced stimulation exhibited better memory for alcohol-related, but not neutral beverage stimuli. CONCLUSIONS: These findings suggest that individual differences in sensitivity to the positive, rewarding effects of alcohol are associated with greater propensity to remember alcohol-related stimuli encountered while intoxicated. As such, stimulant responders may form stronger memory associations with alcohol-related stimuli, which might then influence their drinking behavior.

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).

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.

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.

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.

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.

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.

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.

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.

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).

"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).

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.

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.