Alcohol Cue Exposure Research Articles

Leveraging meta-regression to test if medication effects on cue-induced craving are associated with clinical efficacy.

The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials. To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials. We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints. There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( = 0.253, SE = 0.189,p = 0.090) and abstinence ( = 0.829, SE = 0.747,p = 0.133) in RCTs. The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds.

Neural correlates of increased alcohol demand following alcohol cue exposure in adult heavy drinkers

Alcohol use disorder is associated with overvaluation of alcohol relative to other rewards, in part due to dynamic increases in value in response to alcohol-related cues. In a neuroeconomic framework, alcohol cues increase behavioral economic demand for alcohol, but the neural correlates these cue effects are unknown. This functional magnetic resonance imaging study combined a neuroeconomic alcohol purchase task with an alcohol cue exposure in 72 heavy drinkers with established sensitivity to alcohol cues (51 % female; mean age=33.74). Participants reported how many drinks they would consume from $0-$80/drink following exposure to neutral and alcohol images in a fixed order. Participants purchased significantly more drinks in the alcohol compared to the neutral condition, which was also evident for demand indices (i.e., intensity, breakpoint, Omax, elasticity; ps<0.001; ds=0.46–0.92). Alcohol purchase decisions were associated with activation in rostral middle and medial frontal gyri, anterior insula, posterior parietal cortex, and dorsal striatum, among other regions. Activation was lower across regions in the alcohol relative to neutral cue condition, potentially due to greater automaticity of choices in the presence of alcohol cues or attenuation of responses due to fixed cue order. These results contribute to growing literature using neuroeconomics to understand alcohol misuse and provide a foundation for future research investigating decision-making effects of environmental alcohol triggers.

Impact of a pre-test measurement of alcohol craving in cue-exposure studies: Relationship with social desirability and demand effects

Craving is one of the most studied concepts in the field of addiction. It is often investigated with repeated-measure experimental designs using self-reported scales. However, the explicit nature of self-reported craving scales may make them vulnerable to social desirability and demand effects. The aim of the present study was to test whether a pre-experimental measurement of craving affects its post-experimental assessment after an alcohol video exposure and whether these changes relate to social desirability, demand effects, and alcohol consumption. Seventy-five healthy volunteers aged 18–30 years were randomly assigned to two experimental groups: a pre-post and a post-only craving assessment group. They were invited to watch an alcohol-related video. Social desirability, demand effects, engagement toward the video, and severity of alcohol consumption were assessed in all participants. The results showed a significant effect of alcohol consumption (p < .001, η2p = .09) on post-experimental craving. The main effect of the repeated measure of craving was also significant (p = .04, η2p = .001), together with the interaction between these two variables (p = .03, η2p = .06). The pre-experimental craving measurement increased its post-experimental levels, but only in heavy drinkers. However, no evidence was found that these changes were related to social desirability or demand effects. Additional exploratory analyses indicated that craving increase in high alcohol drinkers was mediated by a stronger engagement toward the alcohol-related video.In summary, the repeated measurement of craving with explicit scales has a significant impact on the results of alcohol craving studies and may not always be desirable, especially when the true purpose of the study needs to be hidden from the participants. However, the present results also suggest that the pre-post experimental design is advisable when the experimenters seek to maximize the relationship between the individual levels of alcohol consumption and alcohol cue-exposure craving changes.

Alcohol cue reactivity in the brain: Age-related differences in the role of social processes in addiction in male drinkers.

Social attunement (SA)-the tendency to harmonize behavior with the social environment-has been proposed to drive the escalation of alcohol use in adolescence, while reducing use in adulthood. Little is known about how heightened social sensitivity in adolescence may interact with neural alcohol cue reactivity-a marker of alcohol use disorder-and its relationship to alcohol use severity over time. The aims of this study were to test whether (1) adolescents and adults differ in social alcohol cue reactivity in the nucleus accumbens, anterior cingulate cortex, and right medial prefrontal cortex (mPFC), and (2) age moderates the relationship between social alcohol cue reactivity and social attunement, measures of drinking at baseline, and changes in drinking over time. A sample of male adolescents (16-18 years) and adults (29-35 years) completed an fMRI social alcohol cue-exposure task at baseline and an online follow-up two to three years later. No main effects of age or drinking measures were observed in social alcohol cue reactivity. However, age significantly moderated associations of social alcohol cue reactivity in the mPFC and additional regions from exploratory whole-brain analyses with SA, with a positive association in adolescents and negative association in adults. Significant age interactions emerged only for SA in predicting drinking over time. Adolescents with higher SA scores escalated drinking, while adults with higher SA scores reduced drinking. These findings warrant further research on SA as a risk and protective factor and suggest that social processes influence cue reactivity differentially in male adolescents and adults.

Cross-substance primed and cue-induced craving among alcohol and cannabis co-users: An experimental psychopharmacology approach.

Co-use of alcohol and cannabis is highly prevalent and often problematic. However, mechanisms underlying their co-use remain unclear. This randomized and crossover study tests cross-substance subjective craving for alcohol and cannabis. A community sample of nontreatment-seeking alcohol and cannabis co-users (N = 30 completers, 40% female) reporting high-risk levels of alcohol and cannabis use completed two experimental sessions in their homes and were monitored remotely using internet meeting technology (i.e., Zoom). The two counterbalanced and randomized sessions were as follows: (a) consumption of a standard alcoholic beverage followed by cannabis cue exposure and (b) consumption (i.e., smoking) of a miniature cannabis cigarette (containing 18%-22% tetrahydrocannabinol), followed by alcohol cue exposure. Participants rated their subjective craving for both alcohol and cannabis at baseline, following alcohol/cannabis administration, and following the presentation of cross-substance-related cues. Repeated measures analysis of variances revealed a statistically significant difference in cannabis craving across time, such that craving for cannabis was significantly higher following cannabis cue reactivity, compared to baseline and following alcohol administration (p's < .001). Similarly, there was a statistically significant difference in alcohol craving across time, such that craving for alcohol was significantly higher following alcohol cue reactivity, compared to baseline and following cannabis administration (p's < .001). Overall, results suggest that individuals who co-use alcohol and cannabis are most sensitive to the cue-induced, rather than the pharmacologically induced effects, of substance administration on cross-substance craving. This pattern of findings does not support a complementarity model. Conversely, these results may be interpreted as indicative of a substitution model for alcohol and cannabis co-use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effects of age on the severity of problem drinking: Mediating effects of positive alcohol expectancy and neural correlates.

Aging is associated with reduction in the severity of alcohol misuse. However, the psychological and neural mechanisms underlying the age-related changes remain unclear. Here, we tested the hypothesis that age-related diminution of positive alcohol expectancy (AE) mediated the effects of age on problem drinking and investigated the neural correlates of the mediating effects. Ninety-six drinkers 21-85 years of age, including social drinkers and those with mild/moderate alcohol use disorder (AUD), were assessed for global positive (GP) AE and problem drinking, each with the Alcohol Expectancy Questionnaire and Alcohol Use Disorders Identification Test (AUDIT), and with brain imaging during alcohol cue exposure. We processed imaging data with published routines; identified the correlates shared between whole-brain regression against age, GP and AUDIT scores; and performed mediation and path analyses to explore the interrelationships between the clinical and neural variables. The results showed that age was negatively correlated with both GP and AUDIT scores, with GP score completely mediating the correlation between age and AUDIT score. Lower age and higher GP correlated with shared cue responses in bilateral parahippocampal gyrus and left middle occipital cortex (PHG/OC). Further, higher GP and AUDIT scores were associated with shared cue responses in bilateral rostral anterior cingulate cortex and caudate head (ACC/caudate). Path analyses demonstrated models with significant statistical fit and PHG/OC and ACC/caudate each interrelating age to GP and GP to AUDIT scores. These findings confirmed change in positive AE as a psychological mechanism mitigating alcohol misuse as individuals age and highlighted the neural processes of cue-reactivity interrelating age and alcohol use severity.

Mindfulness-Oriented Recovery Enhancement: An Evidence-Based Social Work Intervention for Addiction, Stress, and Chronic Pain.

The purpose of this commentary is to update social workers about the evolution of Mindfulness-Oriented Recovery Enhancement (MORE) since the publication of the book Mindfulness-Oriented Recovery Enhancement for Addiction, Stress, and Pain (Garland, 2013, reviewed in Martin, 2022) and to provide a succinct overview of MORE’s clinical outcomes and mechanisms. MORE is an evidence-based social work intervention that unites mindfulness training, cognitive–behavioral therapy (CBT), and positive psychology into an integrative treatment for addiction, stress, and chronic pain. Across weekly MORE sessions, participants learn mindfulness, reappraisal, and savoring techniques to alleviate symptoms, enhance well-being, and strengthen their recovery. MORE draws on principles from social–behavioral learning theory to enhance motivation to practice, maximize therapeutic expectancy, and positively reinforce success experiences to increase participant engagement. Since 2013, MORE has been tested in 11 clinical trials, demonstrating efficacy for clients struggling with addiction and related issues (e.g., psychiatric disorders, chronic pain). The first Stage 1 randomized controlled trial (RCT) of MORE was conducted in a sample of people with alcohol use disorder (many of whom had co-occurring cocaine use disorder) residing in a long-term therapeutic community. This pilot (N = 53) provided an initial indication of MORE’s potential treatment value, demonstrating effects on addiction risk mechanisms including alcohol attentional bias and autonomic recovery from alcohol cue exposure—indicators of the extent to which a patient was “triggered” by addiction cues (Garland et al., 2010). Subsequently, my colleagues and I launched a five-year Stage 3 RCT (N = 180) of MORE at the same therapeutic community in a sample of formerly homeless men with co-occurring substance use disorders, trauma, and psychiatric disorders. MORE outperformed both trauma-focused CBT (a program based on Seeking Safety) and usual care in reducing drug craving and PTSD symptoms (Garland et al., 2016). For these first two trials of MORE, the treatment was targeted for clients in the “action” and “maintenance” stages of change (Prochaska et al., 1992).

Reactivity to combined experimental stress- and alcohol cue-exposure predicts real-life alcohol use and craving in individuals with alcohol use disorder

Reactivity to combined experimental stress- and alcohol cue-exposure predicts real-life alcohol use and craving in individuals with alcohol use disorder

The Moderating Role of Sex in the Relation between Cue-Induced Craving and Resting-State Functional Connectivity in the Salience Network of Non-Clinically Diagnosed Drinkers

Introduction: Previous research indicates a relation between craving and increased connectivity in the resting-state salience network. However, the link between cue-induced craving and connectivity in the salience network remains unclear. Further investigation is needed to understand the effect of sex on the relationship between cue-induced craving and the salience network. We investigated the role of sex in the association between the resting-state functional connectivity (RSFC) salience network and subjective cue-induced craving. Methods: Twenty-six males (mean age = 25.3) and 23 females (mean age = 26.0), with a score of 12 or higher on the alcohol use disorder identification test, were included in the current study. No significant difference in age was observed between males and females. Participants underwent a resting-state MRI scan for 6 min. Following the MRI scan, participants completed an alcohol cue-exposure task for 5.5 min to assess cue-induced craving using the desire to drink alcohol questionnaire. We applied independent component analysis methods to determine functional connectivity within the salience network. Subsequently, we investigated how cue-induced craving is related to the salience network’s RSFC and if this relationship is moderated by sex. Results: The association between the salience network and cue-induced craving was not statistically significant nor did we find a moderating effect for sex. Conclusion: The null findings in the study may be explained by a lack of power. Alternatively, alcohol use sex disparities may be more prevalent in the recreational/impulsive stage, whereas participants in our study were in the later stage of addiction.

Arc controls alcohol cue relapse by a central amygdala mechanism.

Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identified single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.

Discrimination Without Intoxication: The Role of Controlled Processes in the Promotion of Racial Bias After Viewing Alcohol-Related Cues

Viewing alcohol-related cues (e.g., advertisements) is known to promote expressions of racial bias and aggression through the temporary promotion of reflexive or impulsive responding. However, this increased automaticity may be inhibited by thoughtful control of behavior. We examined the role of controlled processes in the suppression of racial bias following alcohol cue exposure across two experiments. Experiment 1 (N = 125) indicated reduced control of behavior promoted greater expressions of racial bias after viewing alcohol-related cues. Experiment 2 (N = 71) replicated these effects, suggesting individuals with lower neural indices of control, indexed by reduced amplitudes of the error-related negativity (ERN), similarly express greater racial bias after viewing alcohol-related cues. These findings replicate previous work suggesting alcohol-related cues promote impulsivity and application of negative racial stereotypes. Yet, whether this automaticity manifests into behavioral expressions of racial bias depends on the availability to engage self-control to inhibit these socially undesirable responses.

Problem drinking and the interaction of reward, negative emotion, and cognitive control circuits during cue-elicited craving

Individuals engage in alcohol consumption to seek reward and/or alleviate negative emotions. The neural processes subserving reward response and negative emotion thus likely play important roles in motivating alcohol use. Cognitive control, in contrast, is thought to regulate these motivational processes to keep drinking in check. As such, the balance between motivational and control processes may determine drinking behavior. Importantly, this balance is likely dictated by individual differences in drinking motives, including positive alcohol expectancy and perceived social isolation. Here, we characterized how the relative strength of the reward, negative emotion, and control circuit activities during alcohol cue exposure predicted alcohol use severity in 71 adult drinkers. Path models were employed to delineate the relationships between the neural, psychological, and drinking measures. We found that positive alcohol expectancy was associated heightened craving and greater activity of the reward relative to cognitive control circuit during cue exposure. The higher this circuit activity difference, the more severe subjects’ drinking. A similar relationship was found for social isolation, craving, activity difference of negative emotion vs. cognitive control circuits, and alcohol use severity. Thus, distinct neural pathways motivate alcohol use through reward seeking and negative emotion. By characterizing the neural circuits underlying cognitive control and motivational processes, the current study sheds light on how positive and negative reinforcement perpetuates problem drinking.

Frontal Neural Activation During Alcohol Cue Exposure is Associated With Cognitive Bias Among Veterans With Alcohol Use Disorder and Traumatic Brain Injury

Alcohol Use Disorder (AUD) continues to be a pervasive problem for U.S. military veterans, and commonly co-occurs with traumatic brain injury (TBI). Cognitive biases and neural activation in the presence of alcohol cues are frequently observed among those with AUD. However, little is known about neural activation during exposure to alcohol cues, implicit cognitive biases, or their associations among treatment seeking veterans with AUD and TBI.

The Effect of Alcohol Cue Exposure on Tobacco-Related Cue Reactivity: A Systematic Review.

To examine the effect of alcohol cue exposure on tobacco-related cravings, self-administration and other measures of tobacco-related cue reactivity. We searched Medline, PsycINFO, Embase, CINAHL and Scopus from inception to May 2020 for articles reporting on a combination of cue reactivity (and/or cross-cue reactivity), alcohol use and tobacco consumption. A semi-quantitative analysis and study quality assessment were performed for the included articles. A total of 37 articles met our inclusion criteria and were included in the systematic review. Most studies (60%) reported that alcohol cue exposure increased tobacco cravings, but only 18% of studies reported that alcohol cue exposure resulted in an increase in ad libitum smoking. There was also substantial heterogeneity between studies due to differences in methodology related to alcohol cue exposure, measures of tobacco cravings, as well as variable participant and study characteristics. Alcohol cue exposure can increase cravings for tobacco. This has important implications for individuals who use both substances but are trying to quit one or both.

Effects of topiramate on neural responses to alcohol cues in treatment-seeking individuals with alcohol use disorder: preliminary findings from a randomized, placebo-controlled trial

Topiramate, a GABA/glutamate modulator, is efficacious in reducing alcohol consumption, though the mechanisms underlying this effect are not well characterized. This study analyzed functional magnetic resonance imaging (fMRI) data from 22 heavy drinkers enrolled in a 12-week placebo-controlled, randomized clinical trial of topiramate to examine the effects of topiramate on alcohol cue-elicited brain responses, craving, and heavy drinking in individuals with DSM-5 alcohol use disorder. Patients were randomized to receive either topiramate (maximal daily dosage of 200 mg/day) or placebo and were administered an fMRI alcohol cue-reactivity task at baseline (before starting medication) and after 6 weeks of double-blind treatment. Analyses compared the topiramate (n = 12) and placebo (n = 8) groups on (1) the change in brain responses during alcohol cue exposure (vs non-alcohol cues) within five a priori regions of interest related to reward—the bilateral and medial orbitofrontal cortex (OFC) and bilateral ventral striatum (VS) and (2) change in craving and heavy drinking days (HDDs) from baseline and scan 2. Topiramate, relative to placebo, reduced alcohol cue-elicited activation of the left VS, bilateral OFC, and medial OFC, alcohol cue-elicited craving, and HDDs between baseline and 6 weeks of treatment. The reduction in alcohol cue-elicited activation in the medial OFC correlated with reductions in craving, and reduced activation in the right VS, right OFC, and medial OFC correlated with the reduction in HDD. This preliminary study provides evidence that topiramate’s attenuation of alcohol cue-elicited brain activation and craving are key elements of the drug’s neurobiological mechanism of action in reducing heavy drinking.

Social Support Effects on Neural Stress and Alcohol Reward Responses.

Social support (SS), or having people to depend on during times of stress, may offer an emotional and neurological buffer to problem drinking. Specifically, SS may modulate reward and stress-related brain responses to mitigate perceptions of alcohol reward and stress. There is limited evidence, however, on this topic and specifically on brain networks that may modulate SS effects on stress and alcohol reward. Here we present a review of the current literature on this topic as well as data from a large community sample of 115 social drinkers. Findings from a novel fMRI task viewing alcohol cue, stress, and neutral images, in separate blocks, while providing ratings on subjective feelings of alcohol craving, stress, and arousal are included. Lower SS significantly predicted greater alcohol craving during alcohol cue and stress conditions, higher baseline levels of stress, and greater arousal in the alcohol cue, relative to neutral condition. Remarkably, individuals with low SS showed greater reward activation (ventral medial prefrontal cortex (VmPFC) and ventral striatum) during alcohol cue exposure, while those with high SS showed no such activation (p<0.001, family wise error corrected at 0.05). Furthermore, individuals with lower SS showed greater stress circuit (VmPFC, dorsal striatum, and periaqueductal gray) activation not observed in the high SS groups. Both groups showed increased amygdala activation under stress condition. The findings support the notion that SS is a powerful modulator of stress response and reward motivation. High SS buffers neural and subjective stress responses, while low SS potentiates greater reward seeking with higher alcohol craving and greater brain activation during alcohol cue exposure. Previous research and current results suggest the need to further explore the role of SS in those at risk of developing alcohol use disorder and assess novel prevention strategies to boost SS in at-risk drinkers.

Slow associative learning in alcohol dependence and the alcohol cue exposure treatment paradox.

To examine two explanations for the observation that cue-exposure treatment has not been clearly effective in the treatment of alcohol dependence: do alcohol-dependent individuals have either (1) slower extinction and/or (2) greater contextual specificity of extinction than non-dependent individuals? In two exploratory laboratory experiments we used mixed factorial designs with two-group between-subjects factors and within-subjects factors corresponding to performance in different parts of a computer-based learning task. University of Southampton psychology research laboratories and two addiction treatment services in the city of Southampton, UK. Experiment 1: 74 (54 female) undergraduates from the University of Southampton (age mean=20.4years). Experiment 2: 102 (40 female) participants from the University of Southampton, the local community, and from two Southampton alcohol treatment services (age mean=41.3years). The Alcohol Use Disorders Identification Test, a 1-week time-line follow-back alcohol consumption questionnaire, the Barratt Impulsiveness Scale (11th edn), and a computerized learning task. Experiment 2 additionally used the 44-item Big Five Inventory, a drug use history checklist, and the Hospital Anxiety and Depression Scale. Experiment 1: light and heavy drinkers did not differ significantly in extinction [extinction block×drinking status interaction, P=0.761, , 95% confidence interval (CI)= (0,0.028)] or on contextual control of extinction [recovery block×drinking status interaction, P=0.514, , 95% CI=(0,0.084)]. Experiment 2: slower extinction in abstinent alcohol-dependent participants compared with light drinkers [extinction block×drinking status interaction, P=0.023, , 95% CI=0,0.069)] but no significant difference on contextual control of extinction [recovery block×drinking status interaction, P=0.069, , 95% CI=(0,0.125)]. Abstinent alcohol-dependent people may have slower extinction learning for alcohol-related cues than non-dependent light drinkers.

Pain and reward circuits antagonistically modulate alcohol expectancy to regulate drinking

Expectancy of physical and social pleasure (PSP) promotes excessive drinking despite the potential aversive effects of misuse, suggesting an imbalance in the response to reward and pain in alcohol seeking. Here, we investigated the competing roles of the reward and pain circuits in PSP expectancy and problem drinking in humans. Using fMRI data during resting (n = 180) and during alcohol cue exposure (n = 71), we examined the antagonistic effects of the reward-related medial orbitofrontal cortex (mOFC) and pain-related periaqueductal gray (PAG) connectivities on PSP expectancy and drinking severity. The two regions’ connectivity maps and strengths were characterized to assess their shared substrates and net relationship with PSP expectancy. We evaluated mediation and path models to further delineate how mOFC and PAG connectivities interacted through the shared substrates to differentially impact expectancy and alcohol use. During resting, whole-brain regressions showed mOFC connectivity in positive and PAG connectivity in negative association with PSP scores, with convergence in the precentral gyrus (PrCG). Notably, greater PAG-PrCG relative to mOFC-PrCG connectivity strength predicted lower PSP expectancy. During the alcohol cue exposure task, the net strength of the PAG vs. mOFC cue-elicited connectivity with the occipital cortex again negatively predicted PSP expectancy. Finally, mediation and path models revealed that the PAG and mOFC connectivities indirectly and antagonistically modulated problem drinking via their opposing influences on expectancy and craving. Thus, the pain and reward circuits exhibit functional antagonism such that the mOFC connectivity increases expectancy of drinking pleasure whereas the PAG serves to counter that effect.

Ashamed and Alone-Risk Factors for Alcohol Craving Among Depressed Emerging Adults.

Comorbid alcohol use and depression have the highest prevalence among emerging adults and are associated with a number of consequences. Self-medication theory posits individuals with depression use alcohol to cope with their negative emotions. Preliminary work has investigated the social context of depression-related drinking and found that solitary drinking is a risky, atypical behaviour in emerging adulthood that is associated with alcohol misuse. However, it is unknown about what is unfolding in the moment that is driving depression-related drinking in solitary contexts. Accordingly, we used an experimental study to examine if shame mediated the association between depression and in-lab alcohol craving. Emerging adults (N=80) completed a shame induction followed by an alcohol cue exposure in either a solitary or social condition. We used moderated mediation to test hypotheses. Consistent with hypotheses, conditional indirect effects supported the mediation of depression and alcohol craving through shame among those in the solitary condition, but not in the social condition. There was no support for guilt as a mediator. Our study demonstrates that shame is a specific emotional experience that contributes to solitary drinking among depressed emerging adults. It is important to use these results to inform interventions that directly target solitary contexts and shame.

Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.

Chronic alcohol use results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic-pituitary-adrenal axis responses, high stress-induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol-related stress arousal changes and that alpha-1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake. Thus, we hypothesized that prazosin would reduce stress-induced craving and improve neuroendocrine and autonomic response to stress and alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. Forty inpatient treatment-seeking alcohol-dependent individuals were randomly assigned to receive placebo (n=18) or 16mg/d, T.I.D., prazosin (n=22) in a double-blind manner, titrated over 2weeks. In weeks 3 to 4 after achieving full dose, patients were exposed to 3 5-minute personalized guided imagery conditions (stress cue, alcohol cue, neutral/relaxing cue), on 3 consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, heart rate, cortisol, and adrenocorticotropic hormone (ACTH) levels were assessed at baseline, following imagery and at repeated recovery timepoints. Prazosin reduced stress cue-induced alcohol craving (p<0.05) and stress- and alcohol cue-induced anxiety (p<0.05) and increased heart rate responses in all imagery conditions (p<0.05). Prazosin lowered basal cortisol and ACTH (p's<0.05) and attenuated stress cue-induced rises in cortisol (p<0.05) versus placebo. Finally, in those without lifetime anxiety disorder, the placebo group showed stress- and alcohol cue-induced increases in cortisol (p's<0.05), while the prazosin group did not. Prazosin may attenuate stress cue-induced alcohol craving and anxiety during early abstinence while improving adrenergic and stress system function, effects which are independent of a history of lifetime anxiety disorders.