Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals

BACKGROUND: Research has shown that exposure to stress/negative affect and to alcohol cues can each increase alcohol craving and relapse susceptibility in alcohol-dependent individuals. However, whether the emotional and physiological states associated with stress-induced and alcohol cue-induced craving are comparable has not been well studied. Therefore, this study examined the craving, emotional, and physiological responses to stress and to alcohol cues in treatment-engaged, 4-week abstinent, alcohol-dependent individuals using analogous stress and alcohol cue imagery methods. METHOD: Twenty treatment-seeking, alcohol-dependent participants (18 males/2 females) were exposed to a brief 5-minute guided imagery procedure that involved imagining a recent personal stressful situation, a personal alcohol cue-related situation, and a neutral-relaxing situation, 1 imagery per session presented in random order. Alcohol craving, anxiety and emotion rating scales, cardiovascular measures, and salivary cortisol were compared across the 3 conditions. RESULTS: Exposure to stress and to alcohol cues each produced significant increases in alcohol craving, anxiety, and negative emotions and decreases in positive emotions. Stress-induced alcohol craving was significantly correlated with increases in sadness, anger, and anxiety ratings, but alcohol cue-induced craving was associated with decreases in positive affect (joy and neutral relaxed state) and increases in anxiety and fear ratings. Furthermore, stress increased systolic and diastolic blood pressure responses, but significant increases in salivary cortisol were only observed in the alcohol cue condition. CONCLUSIONS: Although both stress and alcohol cues produce increases in anxiety associated with alcohol craving, each produced a dissociable psychobiological state involving subjective emotional, cardiovascular, and cortisol responses. These data could have significant implications for understanding the specific psychobiology associated with stress or alcohol cue exposure and their potential effects on alcohol relapse susceptibility.     

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes

Background: Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress‐induced and cue‐induced craving in heavy drinkers by testing single‐nucleotide polymorphisms (SNPs) of the corticotrophin‐releasing hormone binding protein (CRH‐BP) gene and the mu‐opioid receptor (OPRM1) gene. Methods: This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non‐treatment‐seeking heavy drinkers. Results: Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH‐BP gene (rs10055255) moderated stress‐induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue‐induced alcohol craving following the neutral imagery condition. Conclusions: These initial results extend recent preclinical and clinical findings implicating the CRH‐BP in stress‐related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward‐driven alcohol phenotypes. Human laboratory models of stress and cue‐induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples.     

Suppression of the HPA axis stress-response: implications for relapse

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. This symposium explored the potential role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation upon relapse. HPA axis stimulation induces the release of the glucocorticoid cortisol, a compound with profound effects upon behavior and emotion. Altered stress-responses of the HPA axis in abstinent alcohol-dependent subjects, therefore, may influence their affective and behavioral regulation, thus impacting their potential for relapse. Bryon Adinoff began the symposium with a review of HPA axis dysfunction in alcohol-dependent subjects, including recent studies from his lab demonstrating an attenuated glucocorticoid response to both endogenous and exogenous stimulation in one-month abstinent men. Klaus Junghanns presented his work demonstrating that a blunted ACTH or cortisol response to subjective stressors (social stressor or alcohol exposure) is predictive of a return to early drinking. The final two presenters examined the interaction between naltrexone and HPA responsiveness in alcohol-dependent or at-risk subjects, as naltrexone induces an increase in ACTH and cortisol. Falk Kiefer discussed the relationship between basal HPA axis responsivity and clinical outcome following treatment with naltrexone or acamprosate. Plasma ACTH significantly decreased over the course of the study in the placebo group, but not the medication groups [corrected] Lower basal concentrations of ACTH and cortisol were associated with quicker relapse in the placebo group only. Suchitra Krishnan-Sarin described her preliminary work, in which family-history positive (FH+) and family history negative (FH-) subjects were administered naltrexone, followed by an assessment of alcohol-induced craving. The cortisol response to alcohol was significantly and inversely related to craving in the FH+, but not the FH-, subjects. Alterations in HPA axis responsivity may therefore have a negative impact upon clinical outcome in alcohol-dependent subjects, and disinhibition of the axis with medication may have therapeutic potential.     

Cold pressor task reactivity: predictors of alcohol use among alcohol-dependent individuals with and without comorbid posttraumatic stress disorder

BACKGROUND: The association between stress and alcohol dependence has been well established. Abnormalities in stress reactivity and hypothalamic-pituitary-adrenal axis (HPA) function may be involved in the mechanistic connection between stress and the initiation, development, and/or maintenance of alcohol dependence. Posttraumatic stress disorder (PTSD) commonly co-occurs with alcohol dependence and is characterized by HPA axis abnormalities. This study investigated the relationship between subjective and neuroendocrine stress reactivity to the cold pressor task (CPT) and prospective alcohol use among individuals with alcohol dependence, with and without comorbid PTSD. METHODS: Participants were 63 individuals with (a) alcohol dependence only (n=35) or (b) comorbid alcohol dependence and PTSD (n=28). Participants completed the CPT, a widely used physical laboratory stressor. Subjective stress, craving, adrenocorticotrophin (ACTH), and cortisol were measured before, immediately after, and at 5, 30, 60, and 120 minutes after the CPT. Alcohol use during 1 month following testing was also assessed. RESULTS: For the alcohol-only group, change in craving immediately following the CPT and craving during the 120-minute recovery phase were predictive of follow-up alcohol use. For the alcohol/PTSD group, change in craving was not predictive of follow-up use. Baseline drinking was, however, predictive of followup alcohol use for the alcohol/PTSD group. For the alcohol-only group, a blunted ACTH response coupled with a higher change in craving following the CPT was associated with significantly greater frequency and intensity of drinking during the follow-up phase. CONCLUSIONS: These preliminary findings demonstrate significant differences between the alcohol-only and the alcohol/PTSD group in predictors of relapse. For the alcohol-only group, reactivity to an acute laboratory stressor may be predictive of subsequent alcohol use. This was not true for the alcohol/PTSD group. Although preliminary, the findings may help shed light on the mechanistic relationship between stress reactivity and increased risk for alcohol relapse and dependence in individuals with and without other Axis I comorbidity.     

Gender differences in response to emotional stress: an assessment across subjective, behavioral, and physiological domains and relations to alcohol craving

Background:  Women and men are at risk for different types of stress-related disorders, with women at greater risk for depression and anxiety and men at greater risk for alcohol-use disorders. The present study examines gender differences in emotional and alcohol craving responses to stress that may relate to this gender divergence in disorders.
Method:  Healthy adult social drinkers (27 men, 27 women) were exposed to individually developed and calibrated stressful, alcohol-related, and neutral-relaxing imagery, 1 imagery per session, on separate days and in random order. Subjective emotions, behavioral/bodily responses, cardiovascular arousal [heart rate (HR), blood pressure (BP)], and self-reported alcohol craving were assessed.
Results:  Women reported and displayed greater sadness and anxiety following stress than men and men had greater diastolic BP response than women. No gender differences in alcohol craving, systolic BP or HR were observed. Subjective, behavioral, and cardiovascular measures were correlated in both genders. However, for men, but not women, alcohol craving was associated with greater subjective emotion and behavioral arousal following stress and alcohol cues.
Conclusions:  These data suggest that men and women respond to stress differently, with women experiencing greater sadness and anxiety, while men show a greater integration of reward motivation (craving) and emotional stress systems. These findings have implications for the gender-related divergence in vulnerability for stress-related disorders, with women at greater risk for anxiety and depression than men, and men at greater risk for alcohol-use disorders than women.     

An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics

Background: Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. This study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non‐treatment‐seeking alcoholics. Methods: Seventy‐nine alcohol‐dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no‐stress control condition. Stress reactivity was measured with serum adrenocorticotropic hormone and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by 2 subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire at the beginning and end of the laboratory procedure. Results: The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress × cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion: In this well‐controlled clinical laboratory study of non‐treatment‐seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge‐inducing stimulus, and stress had no effect on general alcohol craving.     

A Pilot Trial of the Alpha-1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence

Background:  Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the α-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD.
Methods:  We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number.
Results:  Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions.
Conclusions:  Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial.     

Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients

BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. METHODS: Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. RESULTS: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin.     

Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive‐ and Anxiety‐Like Behaviors in Male and Female Offspring

Background: Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neurobehavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic‐pituitary‐adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre‐existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive‐ and anxiety‐like behaviors in PAE animals. Methods: Male and female offspring from prenatal alcohol (PAE), pair‐fed (PF), and ad libitum‐fed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well‐validated tasks sensitive to differences in depressive‐ and/or anxiety‐like behaviors. Results: We report here that the combination of PAE and CMS in adulthood increases depressive‐ and anxiety‐like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions: These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations.     

Exploring the Relationship Between Depressive and Anxiety Symptoms and Neuronal Response to Alcohol Cues

Background: Depressive and anxiety symptoms tend to co‐occur with heavy drinking. Specifically, their presence may exacerbate the severity and intractability of heavy drinking. Similarly, heavy drinking may increase the risk for and experience of depressive and anxiety symptoms. Although depressive and anxiety symptoms have been significantly correlated with alcohol craving in cue‐exposure paradigms, physiological responses have not always mapped onto emotional responses. Therefore, this study sought to examine the role of depressive and anxiety symptoms using a more basic science approach, through examining functional brain changes. Methods: Seventy nontreatment seeking, heavy drinking adults were recruited through a college campus (n = 45 men; mean age = 22.8). They completed measures of drinking, smoking, depressive symptoms, anxiety symptoms, and a functional magnetic resonance imaging (fMRI) cue‐exposure paradigm. Results: As hypothesized, depressive symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the insula, cingulate, ventral tegmentum, striatum, and thalamus (cluster‐corrected p < 0.05, z = 2.3). Similarly, anxiety symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the striatum, thalamus, insula, and inferior frontal, mid‐frontal, and cingulate gyri (cluster‐corrected p < 0.05, z = 2.3). Conclusions: Significant correlations were found between depressive symptoms, anxiety symptoms, and differential brain activation in response to an alcohol versus an appetitive control cue in an fMRI paradigm. Moreover, the pattern of activation mapped onto expected regions. This study strongly supports the posited relationships between depressive symptoms, anxiety symptoms, and differential brain activation in an alcohol cue‐exposure paradigm with a sample of heavy drinking adults.     

ELECTRORETINOGRAM AND CUE-ELICITED CRAVING IN WITHDRAWN COCAINEDEPENDENT PATIENTS: A REPLICATION

Background: We previously reported that cocaine-dependent patients with a reduced blue cone b wave electroretinogram (ERG) responses had significantly more cue-elicited craving. Methods: A new series of 21 recently withdrawn cocaine-dependent patients completed a craving questionnaire at baseline and following cue exposure; an ERG was also performed. Results: Cocainedependent patients with a blunted ERG blue cone response (<0.5 μV) showed greater increases in craving following cue exposure. When subjects were included from our preliminary study (N = 14), these differences became highly significant. Conclusions: Patients with a reduced ERG response may represent a subgroup more vulnerable to cocaine craving and future relapse.     

Effects of Alcohol Cue Exposure on Response Inhibition in Detoxified Alcohol‐Dependent Patients

Background: There is evidence that exerting self‐control during alcohol craving can diminish performance on subsequent tasks that require self‐control. Based on the resource depletion model (Muraven and Baumeister, 2000), we examined the influence of alcohol cue exposure on detoxified alcohol‐dependent patients’ ability to inhibit ongoing responses. Methods: Twenty alcohol‐dependent patients were randomly assigned to an alcohol‐cue exposure and a control‐cue exposure condition and thereafter had to perform an inhibition task (i.e., stop‐signal task). Results: Participants who sniffed alcohol before performing the inhibition task reported a stronger urge to drink alcohol than the control group that sniffed water. Participants who sniffed alcohol were also impaired in their inhibitory performance but not in their noninhibitory performance on the stop‐signal task. Conclusions: The urge to drink presumably reduced participants' self‐control, and this interfered with their ability to inhibit responding.     

Fluoxetine Attenuates Adrenocortical but Not Subjective Responses to Cocaine Cues

Preclinical data suggest a link between stress reactivity and cocaine self‐administration by rodents. Serotonin appears to modulate the hypothalamic‐pituitary‐adrenal (HPA) axis. We studied the effects of chronic treatment with the serotonin reuptake inhibitor fluoxetine 40 mg/day on subjective and hormonal responses to cocaine cues in 22 subjects participating in a controlled clinical trial for cocaine dependence. Fluoxetine antagonized the cue‐induced increase in cortisol but increased subjects' ratings of the likelihood of cocaine use in response to cocaine cues. Cortisol response to cocaine cues was not related to subjective craving. Activation of the HPA axis by cocaine cues does not appear to be a necessary mediator of cue‐induced craving.     

Attentional bias training and cue reactivity in cigarette smokers

Aims Attentional bias for drug‐related cues has been associated with drug maintenance and relapse. We investigated whether attentional bias for smoking‐related stimuli could be altered using a modified visual probe task in cigarette smokers. We also sought to determine whether changes in attentional bias were associated with changes in subsequent craving and cue reactivity. Participants Male and female (n = 54) current smokers (≥5 cigarettes per day), aged between 18 and 40 years, were recruited from staff and students of the University of Bristol, and from the general population. Design Participants attended a single test session and completed an attentional training procedure in which they were either trained to attend to smoking‐related pictorial stimuli (attend group) or to neutral pictorial stimuli (avoid group). Group allocation was randomized. Measurements Following attentional training, participants underwent a smoking cue exposure procedure in which they were exposed to smoking‐related stimuli. Subjective measures of mood and craving were taken at baseline and before and after cue exposure. Participants then smoked a cigarette and smoking topography was measured. Findings Attentional training increased attentional bias among participants in the attend group, and decreased attentional bias among those in the avoid group. There were also differences between the attend and avoid groups in post‐training changes in craving during exposure to in vivo smoking cues, reflecting greater increases in craving in the attend group, although these effects were observed in males only. Conclusions These data are the first to show alterations in attentional bias for smoking‐related stimuli following a modified visual probe training procedure. Furthermore, post‐training group differences in subjective craving suggest potential clinical utility of training procedures, although these effects may operate only in males. Future research should investigate whether multiple training sessions enhance post‐training reductions in craving and cue reactivity, and the longer‐term persistence of training effects.     

Food cue reactivity and craving predict eating and weight gain: a meta‐analytic review

According to learning‐based models of behavior, food cue reactivity and craving are conditioned responses that lead to increased eating and subsequent weight gain. However, evidence supporting this relationship has been mixed. We conducted a quantitative meta‐analysis to assess the predictive effects of food cue reactivity and craving on eating and weight‐related outcomes. Across 69 reported statistics from 45 published reports representing 3,292 participants, we found an overall medium effect of food cue reactivity and craving on outcomes (r = 0.33, p < 0.001; approximately 11% of variance), suggesting that cue exposure and the experience of craving significantly influence and contribute to eating behavior and weight gain. Follow‐up tests revealed a medium effect size for the effect of both tonic and cue‐induced craving on eating behavior (r = 0.33). We did not find significant differences in effect sizes based on body mass index, age, or dietary restraint. However, we did find that visual food cues (e.g. pictures and videos) were associated with a similar effect size to real food exposure and a stronger effect size than olfactory cues. Overall, the present findings suggest that food cue reactivity, cue‐induced craving and tonic craving systematically and prospectively predict food‐related outcomes. These results have theoretical, methodological, public health and clinical implications.     

Electroretinogram and cue-elicited craving in withdrawn cocaine-dependent patients: a replication.

BACKGROUND: We previously reported that cocaine-dependent patients with a reduced blue cone b wave electroretinogram (ERG) responses had significantly more cue-elicited craving. METHODS: A new series of 21 recently withdrawn cocaine-dependent patients completed a craving questionnaire at baseline and following cue exposure; an ERG was also performed. RESULTS: Cocaine-dependent patients with a blunted ERG blue cone response (<0.5 microV) showed greater increases in craving following cue exposure. When subjects were included from our preliminary study (N = 14), these differences became highly significant. CONCLUSIONS: Patients with a reduced ERG response may represent a subgroup more vulnerable to cocaine craving and future relapse.     

A Clinical Trial with Combined Transcranial Direct Current Stimulation and Attentional Bias Modification in Alcohol‐Dependent Patients

Background

Modifying attentional processes with attentional bias modification (ABM) might be a relevant add‐on to treatment in addiction. This study investigated whether influencing cortical plasticity with transcranial direct current stimulation (tDCS) could increase training effects. tDCS could also help alcohol‐dependent patients to overcome craving and reduce relapse, independent of training. These approaches were combined to investigate effects in the treatment of alcoholism.

Methods

Ninety‐eight patients (analytical sample = 83) were randomly assigned to 4 groups in a 2‐by‐2 factorial design. Patients received 4 sessions of ABM (control or real training) combined with 2 mA tDCS (active: 20 minutes or sham: 30 seconds) over the left dorsolateral prefrontal cortex. Alcohol bias and craving were assessed, and treatment outcome was measured as relapse after 1 year.

Results

Attentional bias scores indicated that during the training only the group with active tDCS and real ABM displayed an overall avoidance bias (p < 0.05). From pre‐ to postassessment, there were no main or interaction effects of tDCS and ABM on the bias scores, craving, or relapse (p > 0.2). However, effects on relapse after active tDCS were in the expected direction.

Conclusions

There was no evidence of a beneficial effect of tDCS or ABM or the combination. Whether the absence of effect was due to issues with the outcome measurements (e.g., lack of craving, high dropout, and unreliable measurements) or aspects of the intervention should be further investigated.     

Bidirectional interactions between acute psychosocial stress and acute intravenous alcohol in healthy men

Background: The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at 2 different times after the stress. Methods: Healthy men (n = 25) participated in 2 sessions: 1 with the Trier Social Stress Test and the other with a nonstressful control task, each followed by infusions of intravenous alcohol (targeting 40 mg% in 5 minutes) and placebo. One group of participants received alcohol within 1 minute of completing the tasks (Alc0, n = 11), followed by placebo 30 minutes later. In the other group (Alc30, n = 14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., anxiety, stimulation, want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions. Results: Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant‐like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the nonstressful condition, stress decreased the stimulant‐like effects of alcohol and “wanting more.” By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased “want more.” In addition, alcohol administered immediately after the Trier Social Stress Test dampened cortisol responses yet prolonged negative subjective responses to the stress. Conclusions: These findings demonstrate that there are bidirectional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual’s pattern of response to alcohol. This study highlights the fact that stress–alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals.     

Effects of topiramate on urge to drink and the subjective effects of alcohol: a preliminary laboratory study

Background:  Topiramate was recently reported to be efficacious in reducing drinking rates and craving among individuals with alcohol dependence in a randomized controlled trial, but dose effects could not be determined. This laboratory study systematically examined the dose-dependent effects of topiramate on cue-elicited craving and other putative mechanisms of its pharmacotherapeutic effects on drinking.
Methods:  Male and female heavy drinkers ( n  = 61) were randomized to 1 of 3 medication conditions (200 mg/d; 300 mg/d; placebo) in a double-blind study. Participants reached the target dose after a 32-day titration period, then were stabilized for approximately 1 week. All then participated in a laboratory assessment of alcohol cue reactivity and of the subjective effects of a moderate dose of alcohol.
Results:  Both doses of topiramate reduced the frequency of heavy drinking during the titration period as compared to placebo. However, topiramate did not affect self-reported craving for alcohol during the titration period, during the cue reactivity protocol, or in response to the alcohol challenge procedure. Topiramate reduced the stimulating effects of alcohol ingestion compared to placebo, but only in the 200 mg group.
Conclusions:  The results of this study support previous findings that topiramate reduces drinking, but the behavioral mechanism underlying this effect does not appear to be attenuation of craving for alcohol as measured using the approaches employed in this study. Rather, the results tentatively suggest that topiramate may exert its beneficial effects by altering the subjective experiences of alcohol consumption. Limitations of the current study are discussed and complementary methods are recommended for future studies, such as the use of behavioral economic paradigms and ecological momentary assessment.