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Neuroinflammation is implicated in the development and maintenance of alcohol use disorder (AUD) and neuroimmune therapeutics show promise in treating AUD. Proinflammatory signaling contributes to progressive elevations in the dysfunction of mood and alcohol craving. The current study sought to examine potential biobehavioral mechanisms of neuroimmune modulation in AUD under experimental conditions. In a community sample of individuals with AUD who completed a placebo-controlled crossover trial of ibudilast, we tested the effect of ibudilast on the relationship between mood states and alcohol craving. Multilevel modeling analyses tested the hypothesis that ibudilast would moderate the effect of positive and negative mood states on alcohol craving during stress and cue exposures. Results revealed that after stress-induction, participants' feelings of depression and happiness were more strongly predictive of their craving for alcohol while taking ibudilast as compared with placebo (

Introduction: Alcohol craving is a highly challenging obstacle to achieve long-term abstinence. Making alcohol use disorder patients timely aware of high-risk craving situations may protect them against relapse by prompting them to mobilize their coping resources. Current advances in wearable and smart-phone technology provide novel opportunities for the development of detecting these situations of heightened risk of craving, by enabling continuous tracking of fluctuations in psychological and physiological parameters. The present study therefore aims to determine the association between self-reported craving and relapses, and between heightened physiological activity. Specifically, we measured cardiovascular and electrodermal activity, and self-reported craving during one hundred days in the daily life of people trying to recover from alcoholism. The secondary aim is to study whether the association between physiology and craving can be strengthened by the inclusion of context related psychological parameters. Methods: An intensive repeated and continuous measures in naturalistic settings case-study design was employed. Ten participants were monitored with wearable bio-sensors and answered multiple questions every three hours on a smartphone app about craving, lapsing and multiple evidence based contextual variables. The association between physiology, craving and lapses was explored using Matthews correlation coefficients both with a current and 3 h lagged design. The contextual variables were included in a decision tree together with the physiological parameters to explore the added effect on the correlation of these contextual variables. Results: The association between lapses and craving was highly different across individuals, varying between a weak to a strong association. The association between cardiovascular activity and heightened self-reported craving was negligible to weak, however with a high specificity, meaning that most craving events were accompanied by increase heart rate. However, the association between electrodermal activity and craving was lower than with cardiovascular activity for most participants, both prior (lagged) and during craving. For two of the participants the association between physiology and craving improved by adding contextual variables, however, precision was too low. Conclusions: People differ strongly in their bodily reactions and psychological experiences during the first months of their addiction treatment. No individual in our study had unique one-to-one mappings between on the one hand physiological or psychological precursors, and on the other hand craving and (re)lapses. Therefore, detecting high risk craving situations with both physiological activity measured with wearables and psychological precursors to alert people specifically for an imminent (re)lapse, does not seem viable on the basis of the current results. We do see an added benefit of using physiology during treatment, as physiology can help start the conversation about possible high risk craving situations during that week. This would also help the counselor to gain added insights into the fluctuating states of the clients, and help to ameliorate the recall bias of clients. The present study showed the possibility and paved the way for future intensive longitudinal designs integrating both physiological, psychological and contextual factors during the challenging and lengthy recovery from addiction.

AIMS: The current study examined the association between pain catastrophizing and alcohol cue-elicited brain activation in individuals with alcohol use disorder (AUD). METHODS: Non-treatment seeking heavy drinkers with AUD (n = 45; 28 males) completed self-report measures of pain catastrophizing and alcohol use/problems as part of a clinical trial of the neuroimmune modulator ibudilast. Participants were randomized to either placebo (n = 25) or ibudilast (n = 20) and completed an functional magnetic resonance imaging (fMRI) scan to assess neural activation to alcohol cues 1week into the medication trial. Multiple linear regression examined whether pain catastrophizing predicted cue-induced activation in a priori regions of interest, namely the dorsal and ventral striatum (VS). An exploratory whole-brain analysis was conducted to assess the relationship between pain catastrophizing and neural alcohol cue reactivity. RESULTS: Pain catastrophizing predicted greater cue-induced activation in the dorsal (b = 0.006; P = 0.03) but not VS controlling for medication. Pain catastrophizing was positively associated with neural activation to alcohol cues in regions including the bilateral thalamus, left precuneus and left frontal pole. CONCLUSION: Greater pain catastrophizing is associated with greater cue-induced neural activation in brain regions sub-serving habits and compulsive alcohol use. These findings provide initial support for a neural mechanism by which pain catastrophizing may drive alcohol craving among individuals with AUD.

The study examined the effect of GTS-201, a low-molecular weight mimetic of brain-derived neurotrophic factor (BDNF) loop 2, on persistent alcohol craving in outbred male and female albino rats with ethanol preference score ~50% developed in the free choice paradigm between 10% ethanol and water over 24 weeks. Both single and subchronic (5 days) injections of GTS-201 in a daily dose of 5 μg/kg reduced alcohol deprivation effect in female, but not in male rats. The possibility of in vivo sex-dependent regulation of modeled alcohol craving with a low-molecular-weight dipeptide mimetic of BDNF loop 2 was demonstrated and sex-related differences in this effect were revealed

OBJECTIVES: Observational studies suggest emotion regulation (ER) as a potential treatment target for problematic college drinking. The primary aim of this laboratory study was to determine whether trait ER strategies would moderate the impact of negative affect induction on alcohol craving in college drinkers. METHODS: Participants were randomly assigned to a neutral (n = 74) or a negative affect induction (n = 76) and reported their craving after the affect inductions. RESULTS: Greater use of drinking to cope and less use of cognitive reappraisal predicted greater alcohol craving after the negative affect induction, but not after the neutral condition. In contrast, emotion suppression did not predict alcohol craving in either condition. CONCLUSION: Our results highlight the role of ER tendencies — particularly the benefits of cognitive reappraisal — on alcohol craving when experiencing emotional distress. Therefore, ER strategies may be an important target for college drinkers to prevent and reduce problematic drinking.

The primary aim is to replicate the finding that experimentally-induced state anxiety influences alcohol choice, in an observational study of naturally-occurring state anxiety. The secondary aim is to test the association between state anxiety and alcohol craving.

This project aims to investigate the effects of state anxiety on alcohol-related behaviours (i.e., alcohol craving, alcohol choice and approach-avoidance tendencies), and explore whether effects differ by drinking-to-cope status using the 7.5% CO2 model of anxiety.

The Behavioral Inhibition System (BIS) and the Behavioral Approach System (BAS) are two motivational systems that are involved in behavioral and emotional reactions to stimuli. The BIS is thought to be activated by conflicting stimuli and is responsible for the defensive approach to dangerous or unpleasant situations, while the BAS is thought to be activated by cues for reward or escape from punishment (Vecchione, Ghezzi, Alessandri, Dentale, & Corr, 2021). These two behavioral systems can be operationalized and measured by the BIS/BAS scale, a trait scale consisting of 24 statements, each scored on a scale of 1 ("very true for me") to 4 ("very false for me") (Carver & White, 1994). Several studies have used this scale to look at the BIS and the BAS in the context of alcohol use disorder (AUD) (Franken, Muris, & Georgieva, 2006; Hamilton et al., 2012; Rieser et al., 2019; Sprah & Novak, 2008). Most of the literature has studied this scale in relation to alcohol consumption; however, few studies have investigated the relationship between these two systems and alcohol craving. This is an important aspect because, for example, studies have found that craving plays an important role in alcohol seeking and consummatory behaviors and higher craving may be a risk factor for relapse, as previously reviewed (Addolorato, Leggio, Abenavoli, & Gasbarrini, 2005; Cavicchioli, Vassena, Movalli, & Maffei, 2020; Seo & Sinha, 2014). Understanding the correlates of alcohol cravings could help provide insight into individual-based prevention and treatment methods for AUD.

Objective: Racial discrimination is a known risk factor for alcohol-related outcomes among young Black American adults. However, vicarious racial discrimination's associations with alcohol-related outcomes and the role of racial identity in these associations remain unknown. This within-subject experiment study tested whether associations of vicarious racial discrimination with alcohol craving and attentional bias differed by three components of racial identity (centrality, private regard, and public regard). Method: Black young adult, at-risk drinkers (N = 51; Mage = 21 [SD = 3.02]; 60% female) completed two vicarious racial discrimination conditions (manipulated by video) followed by alcohol craving and attentional bias tasks. Results: Associations of vicarious discrimination with alcohol craving were exacerbated by high centrality and buffered by high private regard, but did not differ by public regard. No associations of vicarious discrimination with alcohol attention bias were found. Conclusion: Findings highlight the important role of Black racial identity in within-group differences in the impact of vicarious racial discrimination on select implicit indicators of alcohol risk among Black young adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Increasing evidence implicates sleep/circadian factors in alcohol use; however, the role of such factors in alcohol craving has received scant attention. Prior research suggests a 24-hour rhythm in related processes (e.g., reward motivation), but more research directly investigating a rhythm in craving is needed. Moreover, prior evidence is ambiguous whether such a rhythm in alcohol craving may vary by sleep/circadian timing. To examine these possibilities, 36 late adolescents (18–22 years of age; 61% female) with regular alcohol use but without a current alcohol use disorder were recruited to complete smartphone reports of alcohol craving intensity six times a day for two weeks. During these two weeks, participants wore wrist actigraphs and completed two in-lab assessments (on Thursday and Sunday) of dim light melatonin onset (DLMO). Average actigraphically-derived midpoint of sleep on weekends and average DLMO were used as indicators of sleep and circadian timing, respectively. Multilevel cosinor analysis revealed a 24-hour rhythm in alcohol craving. Findings across the sleep and circadian timing variables converged to suggest that sleep/circadian timing moderated the 24-hour rhythm in alcohol craving. Specifically, people with later sleep/circadian timing had later timing of peak alcohol craving. These findings add to the growing evidence of potential circadian influences on reward-related phenomena and suggest that greater consideration of sleep and circadian influences on alcohol craving may be useful for understanding alcohol use patterns and advancing related interventions.

Negative affect may be related to alcohol-related patterns (e.g., craving and problematic alcohol use). Distress intolerance and positive and negative alcohol-related metacognitions may be underlying mechanisms in this link. This study aimed to evaluate the effect of negative affect including depressive, anxious, and stress symptoms on alcohol craving and problematic alcohol use via the paths of distress tolerance and both positive and negative alcohol-related metacognitions. Three hundred men with problematic alcohol use during the abstinence phase completed psychological and clinical measures. Results showed that craving and negative alcohol metacognitions mediated the relationship between negative affect and problematic alcohol use. Negative affect had a direct and positive effect on craving and indirect effect via distress intolerance and positive alcohol metacognitions. In turn, distress intolerance and positive alcohol metacognitions indirectly and positively affected problematic alcohol use via craving. The study indicates that distress tolerance and distinct alcohol metacognitions may be differently related to various patterns of alcohol-related problems, such that alcohol drinkers with high levels of negative affect, distress intolerance, and positive alcohol metacognitions show higher levels of craving, while high negative affect in relation to high negative alcohol metacognitions and alcohol craving is related to the perpetuation of alcohol use or problematic alcohol use. [Abstract copyright: © 2020 John Wiley & Sons, Ltd.]

Introduccion El deterioro del control sobre el consumo del alcohol se ha mencionado con frecuencia en diversas descripciones teoricas relativas al uso nocivo y es un criterio clinico del DSM para el trastorno por uso de alcohol. Las diferencias en la frecuencia con que se admite el deterioro del control se han considerado como un reflejo de la gravedad del problema. Ademas, se ha postulado que la capacidad de poner un limite al consumo de alcohol puede estar mediada por el deseo de consumirlo (craving). Objetivo En este estudio se abordo la relacion entre el deterioro del control, el autoreporte del craving y la gravedad de la dependencia del alcohol en un grupo de bebedores fuertes. Metodo Se realizo un analisis de clases latentes usando las dimensiones del deterioro del control (control percibido, control fallido e intento de control) de 208 bebedores fuertes. Para determinar si las clases identificadas podian representar diferentes formas de gravedad del trastorno se contrasto el modelo mas adecuado con las puntuaciones de la Escala de Dependencia del Alcohol. Ademas, se evaluo la relacion entre los criterios de deterioro del control (utilizando la Escala de Control Deficiente, ECD) y el craving. Resultados Identificamos una solucion de tres clases basada en la gravedad del deterioro de control. En esa solucion se identifico una relacion con el aumento graduado de las puntuaciones de craving y la gravedad de la dependencia entre las clases. Solo los elementos de la ECD que comprenden el control percibido y parcialmente los relacionados con el control fallido, pero no los que evaluan el intento de control, distinguieron el gradiente entre las clases latentes. Discusion y conclusion Este estudio proporciona mas apoyo a la propuesta de un continuum unidimensional de gravedad entre los usuarios de alcohol y refuerza la relacion teorica entre el fenomeno de deterioro del control y el craving

Alexithymia is a vulnerability factor for physical and mental illness that can significantly influence the daily function of alcohol-dependent patients. The aim of this study was to examine the indirect effect of obsessive thoughts and compulsive behaviors involving alcohol craving on the relationship between alexithymia, quality of life (QoL) of psychological well-being and health status. Three hundred and eighty-one outpatients (263 males and 118 females) in treatment for alcohol dependence completed self-report measures of alexithymia, alcohol craving, GHQ-28 (QoL-psychological well-being) and SF-36 (QoL-health status). Males scored significantly higher than females on aspects of alexithymia, and females reported significantly higher levels of alcohol craving. Path analysis showed an indirect effect of alcohol craving on the relationship between alexithymia, QoL-psychological well-being and self-reported QoL-health status for males only. The current study provides important new information about impaired self-reported health status and well-being among male alcohol-dependent treatment seekers with alexithymia.

Background In-laboratory drinking sessions that allow direct assessment of drinking and craving are an emerging method for testing novel pharmacotherapy compounds and behavioral interventions for alcohol use disorders. Despite wide implementation, limited evidence supports the concordance between drinking in the laboratory and in a natural setting. This study examined the relationship between self-reports of drinking prior to and drinking and craving during an alcohol drinking paradigm (ADP). Methods Participants were adult heavy drinkers (N = 64) who participated in a pharmacotherapy study. Participants completed self-report alcohol assessments and a baseline ADP session prior to any medication administration. Alcohol craving was assessed during priming and ad lib ADP phases. Outcomes were the associations of total drinks consumed in-laboratory and summary drinking measures for the 30 days prior to the ADP and reports of maximum drinks (past year and lifetime). Additional outcomes were the association of self-reported drinking and alcohol craving during the ADP and the concordance between self-report and ADP World Health Organization (WHO) drinking classifications. Results Number of drinking days, average drinks per drinking occasion, and lifetime and past-year maximum drinks were all related to drinking in the laboratory. Heavy drinking days were not related to drinking in the laboratory but were associated with ADP craving. Alcohol craving was also associated with other measures of self-reported drinking. There was also a significant association between WHO drinking risk classification and in-laboratory drinking. Conclusions The observed relationships between self-reported drinking and drinking in-laboratory across drinking indices suggest that in-laboratory alcohol consumption may reflect participants' real-world alcohol consumption, supporting the value of laboratory-based drinking paradigms. The demonstrated relationship with self-reported drinking and ADP alcohol craving further supports the value of such paradigms to model key drinking predictors. These results provide support for the validity of laboratory-based paradigms to accurately reflect participants' recent drinking levels.

Budući da pitanje metakognitivnoga aspekta opraštanja sebi nije obuhvaćeno dosadašnjim istraživanjima, u ovome su istraživanju provjereni odnosi opraštanja sebi kao crte, osjećaja srama zbog pijenja, modificiranoga metakognitivnog modela depresivnosti i alkoholne žudnje na uzorku osoba (N = 125) na bolničkome liječenju od ovisnosti o alkoholu. U tu je svrhu predložen prošireni metakognitivni model depresivnosti kojim su se pokušale objasniti povezanosti tih varijabli. Originalni metakognitivni model modificiran je tako da su depresivne ruminacije zamijenjene ruminacijama o pijenju alkohola, a zatim su na taj model nadograđene varijable opraštanja sebi kao crte i osjećaja srama zbog pijenja kao antecedenti te alkoholna žudnja kao ishodišna varijabla. Za testiranje proširenoga metakognitivnog modela depresivnosti koji je prethodno rastavljen u nekoliko parcijalnih modela korištene su višestruke medijacijske analize s paralelnim i serijskim medijatorima. Model je u većoj mjeri potvrđen. Opraštanje sebi ima izravni učinak na osjećaj srama zbog pijenja, neizravni učinak na pozitivna metakognitivna vjerovanja o ruminacijama putem osjećaja srama zbog pijenja te neizravni učinak na ruminacije o pijenju putem osjećaja srama zbog pijenja i pozitivnih metakognitivnih vjerovanja o ruminacijama. Značajan je i izravni učinak opraštanja sebi na interpersonalne i socijalne posljedice ruminacije. Učinak opraštanja sebi na depresivnost u potpunosti se objašnjava medijatorom ruminacija o pijenju, a analize pokazuju i neizravni učinak putem negativnih metakognitivnih vjerovanja o ruminaciji. Otkriven je i neizravni učinak opraštanja sebi na alkoholnu žudnju putem osjećaja srama zbog pijenja i ruminacija o pijenju. Svi navedeni učinci opraštanja sebi na spomenute kriterijske varijable negativnoga su predznaka. Ruminacije o pijenju pokazale su se najznačajnijim prediktorom depresivnosti i alkoholne žudnje. Modificirani metakognitivni model depresivnosti također je potvrđen na uzorku osoba na liječenju od ovisnosti o alkoholu. Rezultati sugeriraju da je opraštanje sebi mnogo adaptivnija opcija za suočavanje s osjećajem srama i izbjegavanje svih drugih potencijalnih negativnih posljedica, kao što su depresivnost i alkoholna žudnja, nego što je to opetovano razmišljanje o percipiranome prijestupu, koje ima suprotan učinak. U drugome su dijelu istraživanja ispitane varijable promjene u žudnji tijekom liječenja i opraštanja sebi kao crte kao prediktori broja dana apstinencije 90 dana nakon otpusta s liječenja. Višekratno mjereni prediktori žudnje te opraštanja sebi kao crte nisu se pokazali statistički značajnima u predikciji broja dana apstinencije. Ovo je istraživanje pružilo nove spoznaje u razumijevanju konstrukta opraštanja sebi i osjećaja srama otkrivajući njihov metakognitivni kontekst. Istraživanje doprinosi i boljemu razumijevanju depresivnosti kod ovisnika o alkoholu sugerirajući da u tretmanu depresivnosti tih osoba treba uzeti u obzir negativni afekt i ruminacije povezane sa samom ovisnošću. Također, rezultati upućuju na to da za uspješnu apstinenciju nije dovoljno biti sklon opraštanju sebi za vlastite prijestupe, kao ni ne osjećati žudnju za alkoholom tijekom liječenja. Prilikom interpretacije rezultata svakako treba uzeti u obzir ograničenja istraživanja koja su detaljno opisana u disertaciji., Since the issue of the metacognitive aspect of self-forgiveness has not been covered by previous research, this study examined the relationships of trait selfforgiveness, feeling of shame related to drinking, modified metacognitive model of depression and alcohol craving in a sample (N = 125) of inpatients during their treatment for alcohol dependence in psychiatric hospital. An extended metacognitive model of depression has been proposed to explain the association of these variables. The original metacognitive model was modified in such a way that depressive ruminations were replaced by ruminations related to drinking alcohol. The variables of trait self-forgiveness and feeling of shame related to drinking were added to model as antecedents, and finally alcohol craving as the outcome variable. Multiple mediation analyses with parallel and serial mediators were used to test the extended metacognitive model of depression previously disassembled into several smaller models. The model is largely validated. Self-forgiveness has an indirect effect on positive metacognitive beliefs about ruminations through feelings of shame related to drinking, and an indirect effect on ruminations about drinking through feelings of shame related to drinking and positive metacognitive beliefs about rumination. The direct effect of self-forgiveness on the interpersonal and social consequences of rumination is also significant. The effect of self-forgiveness on depression is fully explained by the mediator of rumination about drinking, and analyses also show an indirect effect through negative metacognitive beliefs about rumination. The indirect effect of self-forgiveness on alcohol craving through feelings of shame related to drinking and rumination about drinking was also discovered. All the above effects of self-forgiveness on the mentioned criterion variables are of negative sign. Ruminations about drinking have been shown to be the most significant predictor of depression and alcohol cravings. A modified metacognitive model of depression was also confirmed in a sample of individuals on treatment for alcohol dependence. The results suggest that forgiving oneself is a much more adaptive option for dealing with feelings of shame and avoiding all other potential negative consequences such as depression and alcohol craving than it is to repeatedly think about a perceived offense that has the opposite effect. In the second part of the study, the variables of changes in craving during treatment and trait self-forgiveness were examined as predictors of the number of days of abstinence 90 days after discharge from treatment. The repeatedly measured predictor of craving and trait self-forgiveness did not prove statistically significant in predicting the number of days of abstinence. This research provided new insights in understanding the constructs of selfforgiveness and feelings of shame by revealing their metacognitive context. It also contributes to a better understanding of depression in alcohol addicts by suggesting that the treatment of depression in these individuals should take into account the negative affect and rumination associated with the addiction itself. Also, the results suggest that for successful abstinence, it is not enough to be inclined to forgive oneself for one’s own transgressions, nor not to feel alcohol craving during treatment. When interpreting the results, the limitations of the research described in detail in the dissertation should certainly be taken into account.

The main aim of this work was to determine the impact of COMT and DRD2 gene polymorphisms together with temperament and character traits on alcohol craving severity alcohol-dependent persons. The sample comprised of 89 men and 16 women (aged 38±7). For the sake of psychological assessment various analytic methods have been applied like the Short Alcohol Dependence Data Questionnaire (SADD), Penn Alcohol Craving Scale (PACS) or Temperament and Character Inventory (TCI) test. The SNP polymorphism of the analyzed genes was determined by Real Time PCR test. The results showed, that the COMT polymorphismmay have an indirected relationship with the intensity and changes in alcohol craving during abstinence. The DRD2 receptor gene polymorphisms are related with the intensity of alcohol craving. It seems that the character traits like “self-targeting”, including “self-acceptance”, are more closely related to the severity of alcohol craving and polymorphic changes in the DRD2 receptor than temperamental traits. Although this is a pilot study the obtained results appeared to be promising and clearly indicate the link betweengene polymorphisms alcohol craving and its severity.

Objective: This study aimed to determine the benefits and feasibility of using group music therapy based on emotion-regulation skills to treat male inpatients with alcohol dependence (AD).Methods: We recruited male inpatients with alcohol dependence and randomly assigned those eligible for enrollment to either the study group or the control group. The study group received group music therapy along with treatment-as-usual (TAU), while the control group received only treatment-as-usual. Primary outcomes, including anxiety levels, sleep quality, and alcohol craving, were assessed at baseline and after 2 weeks of treatment. Secondary outcomes included feasibility measures such as dropout rates. We evaluated the acceptability of group music therapy based on semi-structured interviews and feedback from patients and therapists.Results: The average attendance rate of the study group patients who underwent group music therapy was 70.77%, and the drop-out rate was 7.69%. Based on intention-to-treat analysis, we found no differences in baseline assessments (p > 0.05). Assessment after 2 weeks of treatment showed that study group patients were less anxious, slept better, and had reduced alcohol cravings than control group patients. However, these differences were not statistically significant. Participants reported that group music therapy made them feel more relaxed and improved their mood.Conclusion: Group music therapy based on emotion-regulation skills is feasible with potential for efficacy and can be used to treat men with alcohol dependence in a closed inpatient environment. Further long-term research is required to gain a better understanding of the efficacy of using group music therapy to treat alcohol dependence.

The data presented in this study are openly available in FigShare at: 10.6084/m9.figshare.14755278 (accessed on 22 August 2021)., To “flatten the curve” of COVID-19 contagion, several countries ordered lockdowns amid the pandemic along with indications on social distancing. These social isolation measures could potentially bring alterations to healthy behavior, including to alcohol consumption. However, there is hardly any scientific evidence of the impact of such measures on alcohol consumption and binge drinking (BD) among young adults, and how they relate to alcohol craving, stress, anxiety, and depression levels. We addressed these questions by conducting a longitudinal study with 146 Portuguese college students—regular binge drinkers (regular BDs), infrequent binge drinkers (infrequent BDs) and non-binge drinkers (non-BDs)—in three moments: before the pandemic (Pre-Lockdown), during lockdown (Lockdown) and 6 months after (Post-Lockdown). Results revealed that regular BDs decreased alcohol use during Lockdown, a change in behavior that was even greater during Post-Lockdown, when regular BDs displayed similar levels of consumption to infrequent/non-BDs. Additionally, alcohol craving and living with friends were predictive of alcohol use during Lockdown, whereas stress, anxiety, and depression symptoms did not contribute to explain changes in drinking behavior. Collectively, the results suggest that BD in young Portuguese college students can be stopped when the contexts in which alcohol intake usually takes place are suppressed, which may have important implications for future prevention and intervention strategies., This study was conducted at the Psychology Research Centre (PSI/01662), School of Psychology, University of Minho, and funded by the Foundation for Science and Technology (FCT) through the Portuguese State Budget [Ref.: UIDB/PSI/01662/2020]. This study was also supported by the project PTDC/PSI-ESP/28672/2017, funded by FCT and the European Regional Development Fund (FEDER). Eduardo López-Caneda and Alberto Crego were supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education, within the scope of the Individual Call to Scientific Employment Stimulus (CEECIND/02979/2018), and the Transitory Disposition of the Decree No. 57/2016, of 29 August, amended by Law No. 57/2017 of 19 July, respectively. Natália Antunes was supported by a fellowship from the FCT (SFRH/BD/146194/2019) and Rui Rodrigues by a fellowship from the Psychology Research Centre, School of Psychology, University of Minho (UMINHO/BID/2021/19).

Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer’s, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.

Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a “two-bottle” as well as a “drinking in the dark” paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.

The aim of this study was to assess the relationship between feeling of shame related to drinking, rumination about drinking, depression and alcohol craving among psychiatric inpatients with alcohol use disorder (AUD). The clinical sample included 71 inpatients (60 male) average age 49.70 years (SD = 9.78) who were hospitalized for AUD treatment disorder in Psychiatric Hospital Rab. Psychological measures included State Shame Scale, Rumination about Drinking Scale, Beck Depression Inventory and Penn Alcohol Craving Scale. The results show that shame related to drinking is associated with rumination about drinking and depression. Rumination about drinking is associated with depression and alcohol craving, and depression is associated with alcohol craving. Rumination about drinking was also significant predictor of depression and alcohol craving. The results suggest that rumination about drinking is significant for understanding depression and alcohol craving among inpatients with AUD. Since both depression and alcohol craving are significant risk factors for relapse after treatment, these finding also suggest that working through rumination as a part of the treatment could improve AUD treatment outcomes.

Introduction: Our study investigated whether discrimination affects psychologi-cal/physiological stress and alcohol craving. Method: Participants (N = 92) were asked to recall and write about (a) a neutral, (b) a negative, or (c) a discriminatory experience in the past and then completed a cue-reactivity procedure assessing their alcohol craving. In addition, we assessed levels of perceived stress before and after the discrimination manipulation, chronic substance use and craving, prior perceived discrimination, and strength of racial/ethnic identity. Results: Results revealed a small effect in which the discrimination condition increased alcohol cue-elicited craving relative to the other conditions. Chronic craving moderated effects of discrimination on cortisol levels. Self-reported stress levels were increased in the discrimination and negative memory conditions relative to baseline. Strength of racial identity served as a protective factor for substance abuse in those who reported chronic high levels of discrimination. Discussion: We discussed the direct link established between acute exposure to discrimination and craving, and experimental evidence for the relationship between discrimination and self-reported stress, but also addressed potential limitations of this work. It is further discussed how some individual differences factors (e.g., chronic craving) predict physiological stress in discriminatory settings. This work underscored the role of racial identity as a protective factor against alcohol abuse in individuals reporting high levels of discrimination.

AimsAlcohol use disorder is highly heterogeneous. One approach to understanding this heterogeneity is the identification of drinker subtypes. A candidate classification consists of reward and relief subtypes. The current study examines a novel self-report measure of reward, relief, and habit drinking for its clinical correlates and subjective response (SR) to alcohol administration.MethodsNon-treatment-seeking heavy drinkers (n = 140) completed the brief reward, relief, habit drinking scale (RRHDS). A subset of this sample (n = 67) completed an intravenous alcohol administration. Individuals were classified into drinker subtypes. A crowdsourced sample of heavy drinkers (n = 187) completed the RRHDS and a validated reward relief drinking scale to compare drinking classification results.ResultsThe majority of the sample was classified as reward drinkers (n = 100), with fewer classified as relief (n = 19) and habit (n = 21) drinkers. Relief and habit drinkers reported greater tonic alcohol craving compared to reward drinkers. Reward drinkers endorsed drinking for enhancement, while relief drinkers endorsed drinking for coping. Regarding the alcohol administration, the groups differed in negative mood, such that relief/habit drinkers reported a decrease in negative mood during alcohol administration, compared to reward drinkers. The follow-up crowdsourcing study found a 62% agreement in reward drinker classification between measures and replicated the tonic craving findings.ConclusionsOur findings suggest that reward drinkers are dissociable from relief/habit drinkers using the brief measure. However, relief and habit drinkers were not successfully differentiated, which suggests that these constructs may overlap phenotypically. Notably, measures of dysphoric mood were better at detecting group differences than measures capturing alcohol’s rewarding effects.

Background Alcohol craving, or the desire to drink alcohol, has been identified as a key experience preceding alcohol use. Alcoholics Anonymous has long claimed that individuals can allay alcohol cravings by eating sweets. Empirical tests of this strategy are limited to a few preclinical studies in rats, and there is no existing experiment testing the acute effect of eating sweets on alcohol cravings in humans. Purpose The current study sought to experimentally test the acute effect of eating sweets on alcohol cravings in a sample with at-risk drinking. Methods After being exposed to an alcohol cue, individuals with at-risk drinking (N = 150) were randomly assigned to eat sweets (n = 60), eat calorie-equivalent bland food (n = 60), or watch a video (n = 30). Caloric amounts were manipulated. Individuals with at-risk drinking were then exposed to a second alcohol cue. Changes in alcohol cravings from after the first to after the second alcohol cue were measured via visual analog scale and heart rate. Results There were no significant between-group differences in changes in alcohol cravings. Caloric amounts did not modify effects. Conclusions Experimental findings did not provide evidence to support the clinical lore that eating sweets can reduce alcohol cravings, albeit only acutely and for those with at-risk drinking. Other empirically supported strategies for managing alcohol cravings (e.g., pharmacotherapies, mindfulness) could instead be promoted.

BACKGROUND: Alcohol craving is common among adolescents, stronger among those with more alcohol-related problems, and predicts drinking levels in their daily lives. Yet, the conditions that predict momentary changes in craving in real time among adolescents remain unclear. OBJECTIVES: This study examined interactive effects of momentary risk-taking propensity and affect on adolescents’ alcohol craving by leveraging ecological momentary assessment (EMA) methods. METHODS: Participants were 29 adolescents ages 15-19 years (55% female; 69% White; 10% Black; 17% Hispanic); 45% met criteria for alcohol dependence. Following a laboratory session that captured self-report and behavioral assessments, including the well-established Balloon Analogue Risk Task (BART: Lejuez et al., 2002), participants completed multiple daily assessments of alcohol craving, positive and negative affect, and risk propensity for approximately one week. Momentary risk propensity was captured in real-world settings via an EMA behavioral task (“Balloon Game”). RESULTS: Mixed-effects models with EMA reports (Level 1) nested within participants (Level 2) revealed the majority (74%) of variability in “Balloon Game” performance was due to within-person, momentary, fluctuations. Greater momentary positive affect predicted increased alcohol craving, but only when participants exhibited heightened risk-taking propensity. Negative affect did not influence the relation between momentary risk-taking and craving. CONCLUSIONS/IMPORTANCE: Momentary fluctuations in positive affect predicted acute increases in craving but only in moments when adolescents demonstrated higher levels of risk-taking propensity, as captured with an EMA-delivered behavioral task. Momentary risk-taking assessments offer new avenues to substantiate dominant theories on the driving mechanisms of craving and alcohol use among adolescents.

Contrary to most theories of alcohol craving, which only consider desires to use, the Ambivalence Model of Craving (AMC) conceptualizes craving bi-dimensionally as the concurrent desires to consume (approach) and desires not to consume (avoid) alcohol. Consistent with the AMC, the Approach and Avoidance of Alcohol Questionnaire (AAAQ) is a 14-item self-reported measure designed to assess alcohol approach and avoidance inclinations. Scores on the AAAQ have been shown to have high reliability and validity in clinical and college student populations, with a two-factor solution emerging in clinical samples of patients with Alcohol Use Disorders (AUDs) and a three-factor solution in samples of college students. However, despite a number of studies examining the use of the AAAQ in clinical and college student samples, to the best of our knowledge there have not been any psychometric evaluations of the AAAQ in community samples. The current study examined the psychometric properties of the AAAQ by examining the factor structure in a community sample (N = 537). Consistent with the results of previous studies utilizing non-clinical samples, a three-factor solution fit the data best and was invariant across gender. Additionally, all three factors were significantly associated with variables of drinking behavior. These results suggest that the AAAQ provides valid and reliable scores that measure approach and avoidance inclinations in community populations.

Background Despite a rich literature on human laboratory paradigms of subjective response (SR) to alcohol, craving for alcohol, and alcohol self-administration, few studies have examined the interplay across these 3 constructs. The present study addresses this gap in the literature by examining the interplay between SR, craving, and self-administration in the human laboratory. Methods Data were culled from a medication study (NCT02026011) in which heavy drinking participants of East Asian ancestry completed 2 double-blinded and counterbalanced experimental sessions. In each experimental session, participants received a priming dose of intravenous (IV) alcohol to a target breath alcohol concentration (BrAC) of 0.06 g/dl and measures of SR (stimulation and sedation) and alcohol craving were collected across rising BrACs. The IV alcohol challenge was immediately followed by a 1-hour alcohol self-administration period. Results Mixed model analyses found a positive and significant relationship between the slope of stimulation and the slope of craving during the alcohol challenge. The relationship between sedation and craving, however, was not significant. The slope of craving during the alcohol challenge significantly predicted a higher number of mini-drinks consumed and lower latency to first drink. Further, mediation analyses found that craving was a significant mediator of the relationship between stimulation and total number of mini-drinks consumed, but the same pattern was not found for sedation. Conclusions Insofar as alcohol self-administration represents the end point of interest for a host of experimental and clinical research questions, the present study suggests that alcohol craving represents a more proximal predictor of self-administration than measures of alcohol-induced stimulation. It is recommended that human laboratory models interpret measures of SR and craving in light of their relative predictive utility for drinking outcomes.

Aims Replicate the previously reported association of elevated alcohol craving, measured by Penn Alcohol Craving Scale (PACS) during residential treatment, with post-treatment relapse and explore whether elevated craving scores 3 months post-treatment are also associated with subsequent relapse. Methods Alcohol craving was assessed with the PACS on admission and at several time points post-treatment in 190 subjects with DSM-IV diagnosis of alcohol dependence admitted to residential treatment. Data about relapse to any drinking (primary outcome measure) was collected at 3, 6, 9 and 12 months after treatment. Cox regression models were used to determine whether PACS scores were associated with relapse. Statistical models were adjusted for meaningful demographic and clinical covariates. Results Follow-up data was available for 149/190 (78%) of subjects. Elevated PACS scores at discharge were associated with increased relapse risk within the first 3 and 12 months after discharge (P = 0.032 and P = 0.045, respectively). Elevated PACS scores at 3 months were associated with increased risk of subsequent relapse within 12 months after treatment in contacted subjects (P = 0.034) and in the intent-to-treat analysis (P = 0.0001). Conclusions Our findings indicate strong association of post-treatment relapse with elevated alcohol craving measured at treatment completion and at 3 months after treatment and justify the use of this measure to guide relapse-prevention efforts.

Emotion dysregulation mediates the effects of stress on drinking among individuals with co-occurring emotional and alcohol use disorders (AUD). The current study examined the effects of cognitive reappraisal (CR), an adaptive emotion regulation strategy, on mechanisms that contribute to drinking (alcohol craving, inhibitory control) among 50 women veterans. In session one, participants were randomized to one of two 50-min “microinterventions”, either to learn a CR coping strategy or receive non-therapeutic psychoeducation control. In session two, all participants underwent a personalized stress induction, after which women in the experimental condition were instructed to use CR to reduce stress, while those in the control group were instructed to sit quietly. Craving and inhibitory control were measured at post-stress induction and after using CR/sitting quietly. Moderating effects of AUD, depression, and PTSD severity were assessed. Craving and inhibitory control improved among women in both conditions (CR or sitting quietly), with no main effect of condition. Condition by AUD severity had a significant interaction effect (b = 0.018, p = .013), whereby women with more severe AUD had greater decreases in craving after sitting quietly, and women with less severe AUD had greater decreases in craving after CR. The opposite pattern was observed for inhibitory control (b = 6.45, p = .004), with women with less severe AUD having greater decreases in inhibitory control after sitting quietly, and women with more severe AUD having greater decreases in inhibitory control after CR. Results highlight CR's immediate effects on alcohol-related outcomes and the important role of symptom severity.

Background Court-mandated substance use disorder (SUD) treatment, compared to nonmandated treatment, has been associated with increased retention and completion. However, due to limitations of previous studies, whether child protective services (CPS) and criminal justice (CJ) mandated treatment improve treatment completion and retention among women in residential treatment remains unclear. Purpose This study investigated differences in treatment completion and progress based on three clinical discharge outcomes (i.e., completer, noncompleter with significant progress, and noncompleter without significant progress). We hypothesized that women mandated by (1) CJ will have a better treatment discharge outcome (i.e., treatment completer and noncompleter with satisfactory progress) compared to women who are CPS mandated; (2) CPS will have a better treatment discharge outcome (i.e., treatment completer and noncompleter with satisfactory progress) compared to nonmandated women. Methods Study staff conducted multinomial logistic regression analyses on data for a diverse sample of 161 women mandated or nonmandated (CJ: N = 71, CPS: N = 66, nonmandated: N = 24) into residential SUD treatment to determine each group's clinically defined treatment discharge outcomes while controlling for covariates. Results Multinomial logistic regression analyses revealed that being mandated by the CJ system predicted being a treatment completer compared to those who were CPS mandated (RR = 9.88, p = .009). The study found no differences in discharge status of completer without satisfactory progress between those who were CPS mandated and those who were CJ mandated or nonmandated. For women mandated by the CPS system compared to nonmandated women, the risk of being a treatment completer relative to noncompleters with satisfactory progress was not significant (RR = 1.08, p = .897). Analyses showed that being mandated by the CJ system predicted an improved clinically defined discharge outcome of treatment completer compared to women who were nonmandated to treatment (RR = 10.74, p = .016). In several of the models, drug and alcohol craving was associated with increased odds of being a noncompleter of treatment without satisfactory progress. Conclusions This study demonstrates that improved treatment completion and discharge status cannot be assumed based solely on being mandated by the CJ or CPS systems. As evidenced by variability in treatment discharge outcomes within and among referral groups, the paper suggests directions for future research.

Aims: Attentional bias (AB), alcohol craving, and anxiety have important implications in the development and maintenance of alcohol use disorder (AUD). The current study aims to test the effectiveness of a Virtual Reality Cue-Exposure Therapy (VR-CET) to reduce levels of alcohol craving and anxiety and prompt changes in AB toward alcohol content.Method: A 49-year-old male participated in this study, diagnosed with severe AUD, who also used tobacco and illicit substances on an occasional basis and who made several failed attempts to cease substance misuse. The protocol consisted of six VR-CET booster sessions and two assessment sessions (pre- and post-VR-CET) over the course of 5 weeks. The VR-CET program consisted of booster therapy sessions based on virtual reality (VR) exposure to preferred alcohol-related cues and contexts. The initial and final assessment sessions were focused on exploring AB, alcohol craving, and anxiety using paper-and-pencil instruments and the eye-tracking (ET) and VR technologies at different time points.Results: Pre and post assessment sessions indicated falls on the scores of all instruments assessing alcohol craving, anxiety, and AB.Conclusions: This case report, part of a larger project, demonstrates the effectiveness of the VR-CET booster sessions in AUD. In the post-treatment measurements, a variety of instruments showed a change in the AB pattern and an improvement in craving and anxiety responses. As a result of the systematic desensitization, virtual exposure gradually reduced the responses to significant alcohol-related cues and contexts. The implications for AB, anxiety and craving are discussed.

Introduction Alcohol cravings can predict relapse in persons with alcohol use disorder (AUD). Consuming sweets is a commonly recommend strategy to quell alcohol cravings in early recovery from AUD, yet research is equivocal on whether consuming sweets mitigates alcohol cravings or relapse risk. The current study used ecological momentary assessment (EMA) data to examine real-time alcohol cravings, sweet cravings, and consumption of sweets among adults in early recovery from AUD. Methods We used EMA methods to follow 25 adults (n = 14 women, 56%; M. age 40, S.D. 10.68) recently discharged from a partial hospitalization program for AUD for 21 days. Prompts were sent to the participants for completion four times per day via a mobile app. EMA data were disaggregated prior to analysis to examine between- and within-person effects. A series of three mixed linear models tested: 1) the contemporaneous effect of sweet and alcohol cravings, 2) alcohol cravings predicting sweet consumption later in the day, and 3) sweet consumption predicting alcohol craving later in the day. Results The results of the first model revealed alcohol cravings were associated with sweet cravings early in recovery. In the second model, no effect occurred between alcohol cravings earlier in the day predicting sweet consumption later in the day. The third model suggested consuming sweets earlier in the day predicted higher alcohol cravings later in the day. Discussion Sweet craving and consumption are associated with alcohol cravings among adults in early recovery from AUD. These findings suggest consuming sweets may increase alcohol cravings. If future studies can replicate this result, consuming sweets in early recovery may emerge as a potential risk for relapse in this population.

The identification of variables that can modulate the efficacy of cue exposure using virtual reality (VR) is crucial. This study aimed to explore determinant variables of cue-elicited alcohol craving and perceived realism (PR) of environments and alcoholic beverages during a VR cue-exposure session among alcohol use disorder (AUD) outpatients. A prospective cohort study was conducted amongst 72 outpatients with AUD from a clinical setting. Alcohol craving experienced during VR exposure and PR of virtual environments and alcoholic drinks were evaluated after a VR session of exposure to alcohol-related contexts and cues. Sociodemographic, psychological and consumption characteristics were examined as possible predicting variables. Multiple linear regression analyses showed that the AUD severity and PR of beverages were predictors of cue-elicited alcohol craving. Educational level, PR of beverages and age were predictors of the PR of VR environments. In relation to the PR of VR beverages, cue-elicited alcohol craving and the PR of environments were predictors. A simple mediational model was also performed to analyze the influence of the PR of beverages on the relationship between the AUD severity and alcohol craving experienced during VR exposure: an indirect or mediational effect was found. PR of alcoholic beverages was (1) a key predictor of the PR of VR environments (and vice versa) and the alcohol craving (and vice versa) experienced during VR cue-exposure sessions using ALCO-VR software among AUD patients and (2) a mediator between AUD severity and cue-elicited alcohol craving.

Aim We sought to elucidate whether stress, peers, and in vivo (i.e., direct) alcohol cues elicit alcohol craving in daily life among adolescents and to test whether individual variation in working memory function and biological sex alters these associations. Methods We leveraged ecological momentary assessment (EMA) to examine momentary associations between stress, peers, and direct alcohol cues with craving, assessed as “urge to drink alcohol,” among 86 male (51.2 %) and female (48.8 %) frequent drinkers (i.e., two or more drinking days per week). Participants were ages 14–24 years (M = 20.7 years, SD = 2.1). Participants completed EMA throughout the day for about one week prior to randomization to a treatment condition for an AUD clinical trial. Pre-registered, secondary analyses focused on craving for assessments when adolescents were not drinking, and assessments occurring after drinking on drinking days were removed. Working memory performance was assessed in the laboratory via the Memory for Words subtest of the Woodcock-Johnson III Tests of Cognitive Abilities. Results Craving was heightened at more stressful moments and when adolescents were with their peers and in the presence of direct alcohol cues. Working memory function was not related to craving but altered the relation of momentary stress, peers, and cues with craving once biological sex-related differences were considered. Females generally had lower craving than males, but working memory function served to buffer against stress-induced craving for males. Conclusions Higher working memory function buffered the in-the-moment relation of stress with alcohol craving for males but not females.

Background/Objective: Determining the predictive variables associated with levels of alcohol craving can ease the identification of patients who can benefit from treatments. This study aimed to describe changes (improvement or no change/deterioration) in alcohol craving levels and explore the predictors of these changes from admission to discharge in outpatients with alcohol use disorder (AUD) undergoing treatment-as-usual (TAU), or treatment-as-usual supplemented with virtual reality cue-exposure therapy (TAU + VR-CET). Method: A prospective cohort study was conducted amongst 42 outpatients with AUD (n = 15 TAU + VR-CET and n = 27 TAU) from a clinical setting. Changes in the levels of alcohol craving between admission and discharge were assessed with the Multidimensional Alcohol Craving Scale. Sociodemographic characteristics (age, gender, education, and socioeconomic and civil status), cognitive-affective behavioral patterns (AUD severity, abstinence duration, psychiatric comorbidity, state anxiety, attentional bias, and substance use), and type of treatment (TAU + VR-CET and only TAU) were also evaluated. Results: The TAU + VR-CET group showed greater changes of improvement in the levels of alcohol craving than the TAU group (χ2 = 10.996; p = 0.001). Intragroup changes in alcohol craving from pre to post-treatment were significant in the TAU + VR-CET group (χ2 = 13.818; p = 0.003) but not within the TAU group (χ2 = 2.349; p = 0.503). The odds of an improvement in any of the craving levels between pre- and post-test was 18.18 (1/0.055) times higher in the TAU + VR-CET group with respect to the TAU group. The use of illicit drugs in the month prior to the test increased the odds of having a positive change by 18.18 (1/0.055) with respect to not having consumed. Conclusions: Including VR-CET in TAU programs may provide benefits in the treatment of AUDs mainly among patients with intense alcohol craving and individuals having used illicit substances prior to treatment This research was funded by the Spanish Ministry of Health, Social Services and Equality, Delegation of the Government for the National Plan on Drugs (FEDER/EU/Project 2016I078: ALCO-VR: Virtual reality-based protocol for the treatment of patients diagnosed with severe alcohol use disorder). The study also received support from AGAUR, Generalitat de Catalunya, 2017SGR1693

Alexithymia is a vulnerability factor for physical and mental illness that can significantly influence the daily function of alcohol-dependent patients. The aim of this study was to examine the indirect effect of obsessive thoughts and compulsive behaviors involving alcohol craving on the relationship between alexithymia, quality of life (QoL) of psychological well-being and health status. Three hundred and eighty-one outpatients (263 males and 118 females) in treatment for alcohol dependence completed self-report measures of alexithymia, alcohol craving, GHQ-28 (QoL-psychological well-being) and SF-36 (QoL-health status). Males scored significantly higher than females on aspects of alexithymia, and females reported significantly higher levels of alcohol craving. Path analysis showed an indirect effect of alcohol craving on the relationship between alexithymia, QoL-psychological well-being and self-reported QoL-health status for males only. The current study provides important new information about impaired self-reported health status and well-being among male alcohol-dependent treatment seekers with alexithymia.

Background: Experimental studies have investigated the effects of physical, psychological and pharmacological stressors (that induce state anxiety) on alcohol outcomes. However, no study has investigated the effects of state anxiety on alcohol outcomes, and the moderating role of drinking to cope (DTC) motives, using the 7.5% carbon dioxide (CO2) challenge. Aims: We aimed to investigate the relationships between state anxiety and alcohol-related outcomes (primarily alcohol choice). We also explored whether DTC motives moderated these relationships. Methods: We conducted two experiments using the 7.5% CO2 challenge (Studies 1 and 2) and an observational study (Study 3) ( ns = 42, 60 and 219, respectively), to triangulate findings. Results: In Study 1, experimentally induced state anxiety increased alcohol choice ( p < .001, ηp2 = .29). This finding was replicated in Study 2, but the effect was weaker ( p = .076, ηp2 = .06). Furthermore, DTC moderated the effect ( p = .013, ηp2 = .11). However, in Study 3 there was no clear evidence of an association between naturally occurring state anxiety and alcohol choice ( b = 0.05, p = .655), or a moderating role of DTC ( b = 0.01, p = .852). Conclusions: Experimentally induced, but not naturally occurring, state anxiety increases alcohol choice, although state anxiety levels were lower in the non-manipulated sample.

Recent evidence indicates that the United States is facing a public health crisis of alcohol misuse and alcohol use disorder (AUD), which has been fueled in part by dramatic rises in binge and heavy drinking and prevalence of AUD in women. Historically, alcohol misuse and AUD have been more prevalent in men than in women. However, recent evidence on data from the past decade shows increases in AUD prevalence rates that are associated with substantially higher binge and heavy drinking and AUD prevalence in women compared to men. This paper first addresses the key roles of stress, trauma, childhood maltreatment, negative affect, and mood and anxiety disorders; sex differences in the presentation of these psychosocial and psychological factors; and their contributions to alcohol misuse, escalation to binge and heavy drinking, and transition to AUD in women. Also examined are potential central and peripheral biological mechanisms by which stressors and traumatic experiences, as well as chronic stress states—including depression and anxiety—may facilitate differential pathways to alcohol misuse, escalation, and transition to AUD in women. Finally, this paper discusses major gaps in the literature on sex differences in these areas as well as the need for greater research on sex-specific pathways to alcohol misuse and transition to AUD, so as to support a more comprehensive understanding of AUD etiology and for the development of new strategies for prevention and treatment of alcohol misuse and AUD in women.

Longer periods of abstinence are shown to enhance response to alcohol cues among alcohol-dependent animals(1–4) and humans(5,6), a phenomenon described as “incubation of craving.” The present work examined the effects of days since last drink on general craving and alcohol-cued craving as it occurs in daily life and explored whether effects were influenced by age and dependence. METHODS: Three samples were combined to include 266 drinkers ranging in age from 14 to 67 years recruited from the community; about half (59.4%) met criteria for alcohol dependence. Drinkers used handheld electronic devices to rate their subjective alcohol craving (assessed as “urge to drink”) and situational context (e.g., presence of visible alcohol cues) at non-drinking times in daily life, with days since last alcohol use culled from timeline follow-back interviews and real-world reports. RESULTS: Drinkers at the lower end of the age range in this sample reported greater intensification of craving with more days of continuous abstinence than drinkers at the upper end of the age range. Age was not related to incubation of cue-elicited craving, in specific, however. For drinkers with dependence, craving when in the presence of visible alcohol cues intensified with more days of continuous abstinence, suggesting craving incubation. CONCLUSIONS: This study builds from important foundational work to demonstrate that incubation of cue-elicited craving occurs in dependent drinkers and applies regardless of age. Inasmuch as craving is a motivational drive that maintains alcohol use(7), understanding factors that influence craving in daily life holds promise for improving clinical care.

BACKGROUND Anger and anger-related traits have been related to alcohol use in both cross-sectional and prospective studies. However, only a small number of studies have experimentally manipulated anger to examine whether the manipulation of anger influences alcohol craving or the relative reinforcing value of alcohol. METHODS Participants (N = 231) recruited through Amazon's MTurk were randomly assigned to a provocation condition or a neutral condition prior to completing both the Alcohol Purchase Task and a self-report measure of alcohol craving. Linear regression analyses were conducted to examine the effects of the anger induction, trait hostility, frequency of alcohol use in the past month, and relevant demographic characteristics (gender, age, income) on alcohol craving and indices of alcohol demand. RESULTS Participants assigned to the provocation condition had greater PMax (B = 0.17, p = 0.012) and breakpoint (B = 0.18, p = 0.006) values, less elastic demand (B = -0.15, p = 0.020), and lower drinking intensity (B = -0.14, p = 0.025) than participants assigned to the neutral condition. Trait hostility was positively related to OMax (B = 0.22, p = 0.001), intensity of demand (B = 0.27, p

The efficacy of short-term treatment with mifepristone (MIFE), a high-affinity, nonselective glucocorticoid receptor antagonist, to reduce ethanol drinking was tested in a rhesus macaque model. Stable individual daily ethanol intakes were established, ranging from 1.6 to 4.0 g/kg per day (n = 9 monkeys). After establishment of chronic ethanol intake, a MIFE dosing regimen that modeled a study of rodent drinking and human alcohol craving was evaluated. Three doses of MIFE (17, 30, and 56 mg/kg per day) were each administered for four consecutive days. Both 30 and 56 mg/kg decreased ethanol intake compared with baseline drinking levels without a change in water intake. The dose of 56 mg/kg per day of MIFE produced the largest reduction in ethanol self-administration, with the average intake at 57% of baseline intakes. Cortisol was elevated during MIFE dosing, and a mediation analysis revealed that the effect on ethanol drinking was fully mediated through cortisol. During a forced abstinence phase, access to 1.5 g/kg ethanol resulted in relapse in all drinkers and was not altered by treatment with 56 mg/kg MIFE. Overall, these results show that during active drinking MIFE is efficacious in reducing heavy alcohol intake in a monkey model, an effect that was related to MIFE-induced increase in cortisol. However, MIFE treatment did not eliminate ethanol drinking. Further, cessation of MIFE treatment resulted in a rapid return to baseline intakes, and MIFE was not effective in preventing a relapse during early abstinence. SIGNIFICANCE STATEMENT: Mifepristone reliably decreases average daily ethanol self-administration in a nonhuman primate model. This effect was mediated by cortisol, was most effective during open-access conditions, and did not prevent or reduce relapse drinking.

Given the significant cost of alcohol use disorder (AUD), identifying risk factors for alcohol seeking represents a research priority. Prominent addiction theories emphasize the role of motivation in the alcohol seeking process, which has largely been studied using preclinical models. In order to bridge the gap between preclinical and clinical studies, this study examined predictors of motivation for alcohol self-administration using a novel paradigm. Heavy drinkers (n = 67) completed an alcohol infusion consisting of an alcohol challenge (target breath alcohol = 60 mg%) and a progressive-ratio alcohol self-administration paradigm (maximum breath alcohol 120 mg%; ratio requirements range = 20-3 139 response). Growth curve modeling was used to predict breath alcohol trajectories during alcohol self-administration. K-means clustering was used to identify motivated (n = 41) and unmotivated (n = 26) self-administration trajectories. The data were analyzed using two approaches: a theory-driven test of a-priori predictors and a data-driven, machine learning model. In both approaches, steeper delay discounting, indicating a preference for smaller, sooner rewards, predicted motivated alcohol seeking. The data-driven approach further identified phasic alcohol craving as a predictor of motivated alcohol self-administration. Additional application of this model to AUD translational science and treatment development appear warranted.

Introduction: Alcohol craving is a key symptom of alcohol use disorder (AUD) and a significant cause of poor treatment outcome and frequent relapse. Craving is supposed to impair executive functions by modulating reward salience and decision-making. Objective: The present study sought to clarify this modulation by scrutinizing reward feedback processing in an experimental decision-making task, which was accomplished by AUD patients in 2 conditions, in the context of induced alcohol craving and in neutral context. Methods: AUD inpatients (N = 40) accomplished the Balloon Analog Risk Task, while their EEG was monitored; counterbalanced across conditions, the tasks were preceded either by craving induction by means of imagery and olfactory alcohol cues, or by neutral cues. Decision choice and variability, and event-related potentials (ERPs) prior to (stimulus-preceding negativity [SPN]) and following (P2a) reward feedback upon decisions, and the outcome-related feedback-related negativity (FRN) were compared between conditions and between patients, who experienced high craving upon alcohol cues (N = 18) and those who did not (N = 22). Results: Upon craving induction (vs. neutral condition), high-craving AUD patients showed less adjustment of decision choice to preceding reward experience and more variable decisions than low-craving AUD patients, together with accentuated reward-associated ERP (SPN and P2a), while outcome-related FRN was not modified by craving. Conclusions: Results support orientation to reward in AUD patients, particularly amplified upon experienced craving, which may interfere with (feedback-guided) decision-making even in alcohol-unrelated context. Craving-accentuated ERP indices suggest neuroadaptive changes of cognitive-motivational states upon chronic alcohol abuse. Together with altered reward-related expectancies, this has to be considered in intervention and relapse prevention.

This study is part of a larger project aiming to develop a virtual reality (VR) software to be implemented as a clinical tool for patients diagnosed with alcohol use disorder (AUD). The study is based on previous research in which we identified factors that elicit craving for alcohol in a sample of AUD patients, and which led to the development of a virtual reality software to be used in cue exposure treatments of alcohol use disorder (ALCO-VR). The main objective of this study was to test the effectiveness of ALCO-VR to elicit cue-induced craving and anxiety responses among social drinkers (SD) and AUD patients. Our secondary objective was to explore which responses (cue-induced craving or anxiety) can best differentiate between AUD patients and the SD group. Method: Twenty-seven individuals (13 AUD patients and 14 SD) participated in this study after giving written informed consent. Their anxiety and alcohol craving levels were measured by different instruments at different stages of the procedure. The VR equipment consisted of Oculus Rift technology, and the software consisted of the ALCO-VR platform. Results: Our data indicate that the ALCO-VR software can elicit responses of anxiety and alcohol craving, especially in the group of AUD patients. The cue-induced anxiety response differentiated AUD patients and the SD group better than the cue-induced craving response. Conclusions: The general interest in applying new technologies to the assessment and treatment of mental health disorders has led to the development of immersive real-life simulations based on the advantages of VR technology. Our study concluded that the ALCO-VR software can elicit anxiety and craving responses and that cue-induced anxiety responses can distinguish between AUD and SD groups better than cue-induced craving. The data on craving and anxiety were assessed consistently by different instruments. In addition, we consider that ALCO-VR is able to ecologically assess cue-induced anxiety and alcohol craving levels during exposure to VR alcohol-related environment This study was supported by the Spanish Ministry of Health, Social Services and Equality, Delegation of the Government for the National Plan on Drugs (FEDER/UE/Project 2016I078: “ALCO-VR: Virtual Reality-based protocol for the treatment of patients diagnosed with severe alcohol use disorder”). The study also received support from AGAUR, Generalitat de Catalunya, 2017SGR1693

Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular the cerebral metabotropic glutamate receptor 5 (mGluR5). Using [18F]FPEB positron emission tomography, it was found that chronic alcohol use leads to decreased limbic mGluR5 availability, where lower mGluR5 was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2- and 6-month of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods: [18F]FPEB scans were performed in 16 recently detoxified alcohol-dependent patients (baseline condition), after 2 months (n = 10) and 6 months (n = 8) of detoxification, in comparison to 32 age- and gender-matched controls. mGluR5 availability was quantified by [18F]FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analysis. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed by a Time-Line Follow Back and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed a sustained recovered mGluR5 availability in cortical and subcortical regions (pheight

Background Multiple measures are utilized to assess alcohol craving, often interchangeably. Little is known about the relationship between tonic and phasic craving. This study fills this gap in the literature by examining the association between tonic levels of alcohol craving and phasic craving for alcohol that is provoked by alcohol administration. Methods Forty-three non-treatment seeking problem drinkers underwent an initial interview and two laboratory testing sessions, where either alcohol or a saline placebo was administered intravenously. Tonic craving was assessed via the Penn Alcohol Craving Scale (PACS) and Obsessive Compulsive Drinking Scale (OCDS) at the initial interview. Phasic craving was assessed during the laboratory sessions (i.e., alcohol and saline administrations, single blinded) at baseline and at 3 subsequent breath alcohol concentrations (0.02, 0.04, and 0.06 g/dl). Results There was a main effect of PACS in predicting phasic craving across both saline and alcohol administration conditions (p 0.10), predicted phasic craving during alcohol, as compared to saline administration. Conclusion In sum, tonic craving captured by the OCDS was predictive of phasic craving during alcohol administration whereas the PACS more generally captured the increase in phasic craving. Therefore, these measures of tonic craving may function differently in capturing the experience of phasic craving. Implications for the utilization of the PACS and OCDS as well as assessments of craving in alcoholism research are discussed., Highlights • Many measures are utilized, often interchangeably, to assess alcohol craving. • Little is known about the relationship between provoked, phasic craving and long-term, tonic craving. • Results indicated that the PACS predicted phasic craving, regardless of alcohol condition. • The OCDS predicted phasic craving when alcohol was administered.

Background: Substance use is known to be episodic, dynamic, complex, and highly influenced by the environment, therefore a situational and momentary focus to alcohol craving research is appropriate. Current advances in mobile and wearable technology provide novel opportunities for craving research. However, the lack of consensus within craving theory impedes the identification and prioritization of parameters to be monitored. The aim of this study is to critically review current craving models in order to determine viable theoretical frameworks of alcohol craving and its essential parameters. Methods: Eighteen models of craving were reviewed by applying a literature search with a five-step strategy that accounted for the momentary nature of craving and included a snowballing search and a key term extraction algorithm. Based on this review, multiple decision criteria were defined upon which to evaluate the models. Results: Six models for alcohol craving were supported by sufficient empirical research to be eligible. The inferences drawn on these six models resulted in three decision criteria: the model should (1) incorporate negative affect as a predictor of relapse; (2) explain that dependent drinkers have a higher attentional bias towards alcohol cues than nondependent drinkers; (3) incorporate increased risk of relapse with heightened stress levels. Conclusions: The affective processing model of negative reinforcement, the cognitive processing model, the incentive sensitization theory of addiction and the theory of neural opponent motivation are classified as viable theoretical frameworks, resulting in negative affect and stress as relevant parameters to include in real-time craving monitoring research.

Background: The role of craving in alcohol dependence and its relationship with relapse has been studied widely in the past decade. The present study was undertaken to assess the role of craving in short-term relapse of patients seeking treatment for alcohol dependence and changes in craving score at the end of detoxification and at follow-up. Materials and Methods: A total of 34 male individuals with alcohol dependence (excluding comorbid drug dependence, organic or psychiatric disorder), after detoxification and discharge, consented. No anticraving medicine, aversive or psychotherapy, was advised. They were diagnosed on the International Statistical Classification of Diseases-10 using Diagnostic Interview for Genetic Studies. Severity of Alcohol Dependence Questionnaire (SADQ) and Clinical Institute Withdrawal Assessment Scale–Alcohol-Revised (CIWA-AR) were administered at the time of admission. Penn Alcohol Craving Scale (PACS) was applied at the time of discharge and follow-up to measure craving for alcohol. Results: Out of a total of thirty patients analyzed after dropout, 21 relapsed at the end of 1 month. On comparing PACS scores between relapsed and nonrelapsed patients, the difference was significant at both time points, i.e., at discharge and follow-up (t = 4.15, P < 0.0001 and t = 4.01, P < 0.001, respectively). In the total sample, SADQ and CIWA-AR scores were positively correlated (r = 0.47, P = 0.009). PACS at discharge was compared with PACS at follow-up, of which the correlation was high (r = 0.832, P < 0.0001). Conclusion: Craving seems to be a main factor related to relapse. Its measurement with PACS can be a useful tool to predict subsequent drinking and to identify individual risk for relapse during treatment.

Introduction A preliminary study showed the existence of a relationship between alcohol craving and insomnia symptoms. The current investigation aimed to further assess the relationship between obsessive and compulsive qualities of alcohol craving and insomnia disorder in a larger sample of subjects with Alcohol Use Disorder (AUD) seeking treatment for their drinking. Methods We used baseline cross-sectional data from a clinical trial of treatment-seeking patients with AUD (N=123). We used the following instruments: Insomnia Severity Index (ISI) total score for insomnia; Obsessive Compulsive Drinking Scale (OCDS) scale scores for alcohol craving; Time-Line follow Back interview for computing the number of drinks per drinking day within the past 90 days; Hamilton Anxiety Rating Scale total score for the anxiety symptoms; and Addiction Severity Index for demographic variables. We used bivariate analysis to evaluate whether alcohol craving outcome measures (OCDS subscale scores and total score) were independently associated with the ISI total score. A multivariable model adjusted for sociodemographic and clinical covariates further evaluated this relationship between OCDS and ISI total scores. Results The mean (SD) age was 44.02 (10.37) years with 13.29 (3.10) years of education, 83.74% were males, 41.80% identified themselves as White, 17.21% were married, and 56.09% were employed. In a bivariate analysis, ISI total score was associated with the obsessive subscale (β=0.25, p Conclusion This study not only confirmed that alcohol craving was associated with insomnia in a larger sample but also demonstrated that insomnia is linked to both obsessive thoughts about alcohol use and compulsive drinking behavior, especially its obsessive aspect. These findings add to the growing literature on the relationship between a pathologic drive for alcohol use and abnormal wakefulness. Support (if any) The study was supported by VA grant IK2CX000855 (S.C.) and NIH grants R01 AA016553 (K.M.K.).