Alcohol Cues Research Articles

Predictive utility of the P3 event-related potential (ERP) response to alcohol cues for ecologically assessed alcohol craving and use.

Neural measures of alcohol cue incentive salience have been associated with retrospective reports of riskier alcohol use behaviour and subjective response profiles. This study tested whether the P3 event-related potential (ERP) elicited by alcohol-related cues (ACR-P3) can forecast alcohol use and craving during real-world drinking episodes. Participants (N =262; Mage = 19.53; 56% female) completed a laboratory task in which they viewed images of everyday objects (Neutral), non-alcohol drinks (NonAlc) and alcohol beverages (Alc) while EEG was recorded and then completed a 21-day ecological momentary assessment (EMA) protocol in which they recorded alcohol craving and consumption. Anthropometrics were used to derive estimated blood alcohol concentration (eBAC) throughout drinking episodes. Multilevel modelling indicated positive associations between P3 amplitudes elicited by all stimuli and within-episode alcohol use measures (e.g., eBAC, cumulative drinks). Focal follow-up analyses indicated a positive association between AlcP3 amplitude and eBAC within episodes: Larger AlcP3 was associated with a steeper rise in eBAC. This association was robust to controlling for the association between NonAlcP3 and eBAC. AlcP3 also was positively associated with episode-level measures (e.g., max drinks, max eBAC). There were no associations between any P3 variables and EMA-based craving measures. Thus, individual differences in neural measures of alcohol cue incentive salience appear to predict the speed and intensity of alcohol consumption but not reports of craving during real-world alcohol use episodes.

Augmenting glutamatergic, but not dopaminergic, activity in the nucleus accumbens shell disrupts responding to a discrete alcohol cue in an alcohol context.

Discrete alcohol cues and contexts are relapse triggers for people with alcohol use disorder exerting particularly powerful control over behaviour when they co-occur. Here, we investigated the neural substrates subserving the capacity for alcohol-associated contexts to elevate responding to an alcohol-predictive conditioned stimulus (CS). Specifically, rats were trained in a distinct 'alcohol context' to respond by entering a fluid port during a discrete auditory CS that predicted the delivery of alcohol and were familiarized with a 'neutral context' wherein alcohol was never available. When conditioned CS responding was tested by presenting the CS without alcohol, we found that augmenting glutamatergic activity in the nucleus accumbens (NAc) shell by microinfusing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced responding to an alcohol CS in an alcohol, but not neutral, context. Further, AMPA microinfusion robustly affected behaviour, attenuating the number, duration and latency of CS responses selectively in the alcohol context. Although dopaminergic inputs to the NAc shell were previously shown to be necessary for CS responding in an alcohol context, here, chemogenetic excitation of ventral tegmental area (VTA) dopamine neurons and their inputs to the NAc shell did not affect CS responding. Critically, chemogenetic excitation of VTA dopamine neurons affected feeding behaviour and elevated c-fos immunoreactivity in the VTA and NAc shell, validating the chemogenetic approach. These findings enrich our understanding of the substrates underlying Pavlovian responding for alcohol and reveal that the capacity for contexts to modulate responding to discrete alcohol cues is delicately underpinned by the NAc shell.

A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder

Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting an estimated 283 million individuals worldwide, with substantial health and economic consequences. Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, have shown promise in preclinical studies as potential therapeutic targets for AUD. In this human laboratory study, we aimed to translate preclinical findings on the PPAR-α agonist fenofibrate to a human population with current AUD. We hypothesized that, relative to placebo, fenofibrate at the highest FDA-approved dose of 145 mg/d would attenuate responsiveness to in vivo alcohol cues in the lab and reduce drinking under natural conditions. However, the results did not show significant differences in craving and alcohol consumption between the fenofibrate and placebo groups. Reverse translational studies in rodent models confirmed the lack of fenofibrate effect at human-equivalent doses. These findings suggest that inadequate translation of drug dose from rodents to humans may account for the lack of fenofibrate effects on alcohol craving and consumption in humans with AUD. The results highlight the need for new brain-penetrant PPAR-α agonists to adequately test the therapeutic potential of PPAR-α agonists for AUD, and the importance of reverse translational approaches and selection of human-equivalent doses in drug development.

Effect of menstrual cycle on rewarding properties of alcohol cues in women.

Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse from abstinence-based treatments. One potential mechanism underlying this disparity is ovarian hormone fluctuations across menstrual cycle phases, particularly estradiol (E2). Preclinical and clinical studies have shown that E2 levels positively correlate with alcohol consumption, suggesting E2 modulates drinking. Rewarding properties of alcohol are thought to mediate this relationship. The present study tested the degree to which women report increased rewarding effects from alcohol and heightened attention to alcohol-related cues when E2 was elevated during the late follicular phase of the menstrual cycle. Fifty women aged 21-29 participated in a within-subjects placebo-controlled study examining how menstrual cycle phase alters the rewarding properties of alcohol and alcohol-associated cues when sober and intoxicated, as measured by their attentional bias toward alcohol-associated cues and subjective reports. Measures were obtained following 0.60 g/kg alcohol and placebo during the early follicular phase when E2 was low and the late follicular phase (i.e., ovulation) when E2 was elevated. Attentional bias to alcohol-associated cues was greater during the late follicular phase in both sober and intoxicated states. Women reported rewarding effects from alcohol, but no effects of phase were observed. The findings suggest that the rewarding properties of alcohol-associated cues might be enhanced during the late follicular phase of the menstrual cycle when E2 is elevated, possibly increasing the risk for excessive drinking in women during this phase. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Co‐occurring BD and AUD associated with increased craving

Researchers studied reward circuitry dysfunction, which may be a mechanism of co‐occurring bipolar disorder (BD) and alcohol use disorder (AUD), using functional magnetic resonance imaging (fMRI). The objective was to find out how alcohol cue processing differs in people with co‐occurring BD and AUD compared with people who have either one of the disorders. They used a visual alcohol cue reactivity paradigm following one week or more of abstinence from alcohol and other drugs. They rated past‐week mood symptoms for depression and mania, as well as obsessive‐compulsive drinking and impulsiveness. Function MRI was analyzed focusing on the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. The researchers analyzed associations between cue reactivity and select behavioral correlates, namely, alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion and days since last alcohol drink). Of the 112 participants, 28 (25.0%) had BD and AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean age was 38.7 years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Individuals with BD and AUD exhibited reduced activation compared with all other groups. Other groups did not significantly differ from one another. The hypo‐activations were associated with increased impulsivity and obsessive‐compulsive alcohol craving exclusively among individuals with BD and AUD. The researchers concluded that the potential interaction between BD and AUD blunted the response to rewards and decreased inhibitory control. They added that reduced right inferior frontal gyrus and insula alcohol cue reactivity is a novel biomarker of comorbid BD and AUD that may respond to pharmacological interventions targeting impulsivity‐related neural mechanisms for improved executive control. The study, “Alcohol Cue Processing in Co‐Occurring Bipolar Disorder and Alcohol Use Disorder, is by William H. Mellick, Ph.D., and colleagues, and was conducted at the Medical University of South Carolina, Addiction Sciences Division and published Nov. 1 in JAMA Psychiatry.

Cannabis craving in response to alcohol cues in the laboratory and in daily life among adolescents ages 15-17 years.

Most adolescents who drink alcohol also use cannabis, and adolescents who use both substances experience worse long-term outcomes than adolescents who use only one or the other. Recent clinical trials with adolescents and emerging adults show that alcohol cues are associated with elevated cannabis craving in the natural environment but not in the laboratory, highlighting cross-cue reactivity as a potential intervention target. This study extends this work to a younger sample of adolescents at an earlier stage of substance use to examine the generalizability of prior findings and inform etiological mechanisms. Participants were 81 adolescents aged 15-17 years who endorsed past-month alcohol and lifetime cannabis use. They completed a laboratory cue reactivity protocol where they rated their cannabis craving during alcohol cue and control conditions. They also completed 24 days of ecological momentary assessment where they reported multiple times per day on their cannabis craving and whether alcohol cues were visible. Mixed models demonstrated lower cannabis craving following alcohol cue presentation in the laboratory compared to control cues, but higher cannabis craving during moments when alcohol was visible in daily life compared to moments when alcohol was not visible. Frequency of cannabis use at baseline was associated with greater cannabis craving in the laboratory and in daily life regardless of cue type or alcohol visibility, and cannabis craving following alcohol cue presentation in the laboratory was positively related to daily life cannabis craving across contexts. This study adds to prior work suggesting that daily life cannabis craving is elevated when alcohol cues are visible. This cross-cue reactivity may be one factor that drives and maintains alcohol and cannabis use in adolescence.

Alcohol cues increase behavioral economic demand and craving for alcohol in nontreatment-seeking and treatment-seeking heavy drinkers.

Behavioral economic research has revealed significant increases in alcohol demand following exposure to alcohol-related cues. Prior research has focused exclusively on nontreatment-seeking heavy drinkers, included only male participants, or used heterogeneous methods. The current studies sought to replicate and extend existing findings in treatment-seeking and nontreatment-seeking heavy drinkers while also examining sex effects and moderation by alcohol use disorder (AUD) severity. Study 1 included 117 nontreatment-seeking heavy drinkers (51.5% women; M age 34.69; 56.4% AUD+), and Study 2 included 89 treatment-seeking heavy drinkers with AUD (40.4% women; M age = 41.35). In both studies, alcohol demand was measured using a hypothetical alcohol purchase task (APT), and subjective alcohol craving was measured using visual analog scales. Measures were collected following exposure to neutral (water) cues in a standard room and alcohol cues in a bar lab. Alcohol demand (intensity, Omax , breakpoint, and elasticity) and craving were significantly increased following alcohol cues compared to neutral cues (ps < 0.005) with effect sizes ranging from small to large (ηp 2 = 0.074-0.480). Participants with AUD (Study 1) or with higher AUD severity (Study 2) reported higher craving and higher demand for most indices (i.e., main effects; ps < 0.032, ηp 2 = 0.043-0.239). A larger alcohol cue increase in Omax was found for AUD+ participants in Study 1 compared to non-AUD participants (p = 0.028, ηp 2 = 0.041) but not for any other indices in Study 1 or Study 2. There were no significant sex effects. These findings replicate and extend prior research by offering additional insight into alcohol cue effects on the reinforcing value of alcohol and subjective motivation to drink. The results also suggest that sex and AUD severity do not meaningfully impact cue effects across most indices of demand.

People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment.

Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD's neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their "real world" drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder

BackgroundStress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. MethodsNeural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. ResultsCompared with both control conditions, psychosocial stress elicited higher alcohol cue–induced activation in the left anterior insula (familywise error–corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate–corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate–corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate–corrected p = .046). ConclusionsResults indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

I spy with my little eye: An eye-tracking study examining adolescents’ attention to alcoholic and non-alcoholic beverages in Instagram stories

Social media users are frequently exposed to alcohol images on Instagram, which in turn influences their own alcohol behaviors. Yet, it is unclear what factors drive attention to alcohol cues. In an eye-tracking study (N = 108; Mage = 16.54), we examined adolescents' attention to Instagram Stories depending on: (a) the type of beverage depicted (beer vs water), (b) the character-product interaction portrayed (CPI: peers in images shown consuming [high CPI] vs holding beverages [low CPI]) and, (c) participant's own susceptibility (high vs low-risk alcohol drinker). Our results illustrated that adolescents allocated an equal amount of attention to beer and water depicted in Instagram images. Furthermore, they devoted more attention to Instagram images wherein peers were shown consuming water and beer (high CPI) compared to those wherein peers were holding these beverages (low CPI). Surprisingly, high-risk alcohol drinkers were more responsive to both beer and water cues than low-risk drinkers. This was particularly the case for Instagram images with high CPI. These findings have implications for how health cues on Instagram are attended to and processed.

Alcohol Cue Processing in Co-Occurring Bipolar Disorder and Alcohol Use Disorder

Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional magnetic resonance imaging (fMRI) research represents the first evaluation of alcohol cue reward processing in BD + AUD. To determine how alcohol cue processing in individuals with BD + AUD may be distinct from that of individuals with AUD or BD alone. This cross-sectional case-control study (April 2013-June 2018) followed a 2 × 2 factorial design and included individuals with BD + AUD, AUD alone, BD alone, and healthy controls. A well-validated visual alcohol cue reactivity fMRI paradigm was administered to eligible participants following their demonstration of 1 week or more of abstinence from alcohol and drugs assessed via serial biomarker testing. Study procedures were completed at the Medical University of South Carolina. Analysis took place between June and August 2022. Past-week mood symptoms were rated by clinicians using the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. The Alcohol Dependence Scale, Obsessive-Compulsive Drinking Scale, and Barratt Impulsiveness Scale were included questionnaires. Functional MRI whole-brain data were analyzed along with percent signal change within a priori regions of interest located in the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. Exploratory analyses of associations between cue reactivity and select behavioral correlates (alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion, and days since last alcohol drink) were also performed. Of 112 participants, 28 (25.0%) had BD + AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean (SD) age was 38.7 (11.6) years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Whole-brain analyses revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions of the right inferior frontal gyrus and insula. Region of interest analyses revealed a main association of BD (F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD + AUD exhibited reduced activation compared with all other groups who did not significantly differ from one another. These hypoactivations were associated with increased impulsivity and obsessive-compulsive alcohol craving exclusively among individuals with BD + AUD. The findings of this study suggest conceptualizing reward dysfunction in BD + AUD by the potential interaction between blunted reward responsivity and deficient inhibitory control may help guide treatment development strategies. To this end, reduced right inferior frontal gyrus and insula alcohol cue reactivity represents a novel candidate biomarker of BD + AUD that may respond to pharmacological interventions targeting impulsivity-related neural mechanisms for improved executive control.

Electrophysiological Markers of Aberrant Cue-Specific Exploration in Hazardous Drinkers.

Hazardous drinking is associated with maladaptive alcohol-related decision-making. Existing studies have often focused on how participants learn to exploit familiar cues based on prior reinforcement, but little is known about the mechanisms that drive hazardous drinkers to explore novel alcohol cues when their value is not known. We investigated exploration of novel alcohol and non-alcohol cues in hazardous drinkers (N = 27) and control participants (N = 26) during electroencephalography (EEG). A normative computational model with two free parameters was fit to estimate participants' weighting of the future value of exploration and immediate value of exploitation. Hazardous drinkers demonstrated increased exploration of novel alcohol cues, and conversely, increased probability of exploiting familiar alternatives instead of exploring novel non-alcohol cues. The motivation to explore novel alcohol stimuli in hazardous drinkers was driven by an elevated relative future valuation of uncertain alcohol cues. P3a predicted more exploratory decision policies driven by an enhanced relative future valuation of novel alcohol cues. P3b did not predict choice behavior, but computational parameter estimates suggested that hazardous drinkers with enhanced P3b to alcohol cues were likely to learn to exploit their immediate expected value. Hazardous drinkers did not display atypical choice behavior, different P3a/P3b amplitudes, or computational estimates to novel non-alcohol cues-diverging from previous studies in addiction showing atypical generalized explore-exploit decisions with non-drug-related cues. These findings reveal that cue-specific neural computations may drive aberrant alcohol-related decision-making in hazardous drinkers-highlighting the importance of drug-relevant cues in studies of decision-making in addiction.

Approach avoidance training versus Sham in veterans with alcohol use disorder: protocol for a randomized controlled trial

BackgroundAlcohol use disorder (AUD) is highly prevalent and commonly co-occurs with other psychiatric disorders among Veterans. Provisional evidence supports the use of Approach Avoidance Training (AAT) - a form of computer-delivered cognitive bias modification designed to target implicit approach bias for alcohol-related cues - as an adjunctive program to treat AUD. However, the extent to which AAT is effective for improving AUD recovery outcomes in outpatient Veteran samples and those with psychiatric comorbidities has been understudied to date. Here we describe a double-blind randomized controlled trial of AAT versus a comparison condition (Sham) being conducted in Veterans with comorbid psychiatric conditions completing outpatient standard care.MethodsOne hundred thirty-six Veterans currently receiving outpatient treatment for AUD will be recruited for this randomized controlled trial with parallel group assignment. Participants will be randomized to either 6 weeks of AAT (n = 68) or Sham (n = 68) training in conjunction with usual care. Assessments will occur at baseline and 6 weeks, 3 months, and 6 months post-baseline. Primary outcome variables will include functional consequences of drinking. Secondary outcome variables will include alcohol consumption, and behavioral indicators of alcohol approach bias. A subset of participants (n = 51) will also complete functional magnetic resonance imaging (fMRI) to assess neural response during an alcohol approach bias assessment.DiscussionThis study is the first randomized controlled trial of AAT administered as an adjunctive treatment to standard care in Veterans with AUD and comorbid psychiatric disorders. Additionally, behavioral and neuroimaging data will be used to determine the extent to which AAT targets approach bias for alcohol cues. If effective, AAT may be a promising low-cost adjunctive treatment option for individuals with AUD.Registry nameAAT for Alcohol Use Disorder in Veterans.Trial registrationClinicalTrials.gov: NCT05372029; Date of Registration: 5/9/2022.

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

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

Subjective response to alcohol: Interactive effects of early life stress, parental risk for mood and substance use disorders, and drinking context

Early life stress, specifically childhood maltreatment, and parental risk for mood and substance use disorders (SUDs) are associated with increased risk for alcohol use disorder (AUD). There is limited data on how these factors interact to contribute to alcohol-related outcomes. Prior work has suggested early life stress may increase sensitivity to psychostimulants and that subjective response to alcohol is heritable. It is unclear if early life stress alters sensitivity to alcohol and interacts with parental risk for mood/SUDs, which in turn may act as a risk factor for AUD. The current study uses within-subjects placebo-controlled alcohol administration methods to investigate the effects of childhood maltreatment on subjective response to alcohol in young adults with and without parental risk of mood/SUDs. Additionally, we explored interactions with drinking context (i.e., drinking in a bar vs. non-bar context). Within individuals with parental risk for mood/SUDs, there was a positive relation between total Childhood Trauma Questionnaire (CTQ) score and how drunk individuals reported feeling across both alcohol and placebo conditions (parental risk group-by-CTQ interaction p = .01; main effect of CTQ within individuals with parental risk for mood/SUDs p = .005). When exploring interactions with drinking context (bar vs. non-bar context), we observed a significant drinking context-by-parental risk-by-CTQ interaction (p = .03), with CTQ score positively associated with greater positive valence/positive arousal feelings in the parental risk group if they consumed their beverages in the bar context (p = .004) but not if they consumed their beverages in the non-bar context. Results suggest childhood maltreatment may contribute to variation in subjective response to the positive effects of alcohol—possibly mediated by alcohol cues and/or expectancies—in young adults with parental risk for mood/SUDs.

IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers

Objective and designPreclinical studies suggest learned immune system responses to alcohol cues and consumption may contribute to alcohol's pharmacodynamic properties and/or Alcohol Use Disorder (AUD) pathogenesis. Mechanistically, these immune alterations may be associated with increased craving and alcohol consumption, both acutely and over time. We sought to characterize this relationship in a randomized, counter-balanced, crossover neuroimaging experiment which took place between June 2020–November 2021. MethodsThirty-three binge drinkers (BD) and 31 non-binge, social drinkers (SD), matched for demographic and psychological variables, were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for acute alcohol. Craving measures and blood cytokine levels were collected repeatedly during and after scanning to examine the effects of alcohol cues and alcohol consumption on craving levels, Tumor necrosis factor alpha (TNF-α), and Interleukin 6 (IL-6) levels. A post-experiment one-month prospective measurement of participants’ “real world” drinking behavior was performed to approximate chronic effects. ResultsBD demonstrated significantly higher peak craving and IL-6 levels than SD in response to alcohol cues and relative to water cues. Ventromedial Prefrontal Cortex (VmPFC) signal change in the alcohol-water contrast positively related to alcohol cue condition craving and IL-6 levels, relative to water cue condition craving and IL-6 levels, in BD only. Additionally, peak craving and IL-6 levels were each independently related to ATT alcohol consumption and the number of drinks consumed in the next month for BD, again after controlling for craving and IL-6 repones to water cues. However, TNF-α release in the alcohol cue condition was not related to craving, neural activation, IL-6 levels, immediate and future alcohol consumption in either group after controlling for water cue condition responses. ConclusionsIn sum, BD show greater craving and IL-6 release in the alcohol cue condition than SD, both of which were associated with prefrontal cue reactivity, immediate alcohol consumption, and future alcohol consumption over the subsequent 30 days. Alcohol associated immune changes and craving effects on drinking behavior may be independent of one another or may be indicative of a common pathway by which immune changes in BD could influence motivation to consume alcohol. Trial registrationClinical Trials NCT04412824.

Cannabis craving in response to alcohol cues among adolescents and young adults in the laboratory and in daily life.

Cannabis use among adolescents and young adults who drink alcohol is prevalent and relates to poorer clinical outcomes. Interrelated factors, such as cross-reactivity to alcohol cues, may contribute to the high prevalence of cannabis use among young persons who drink alcohol. We tested whether systematic presentation of alcohol cues in the laboratory and naturalistic presence of alcohol cues in daily life elicit cannabis craving. Data were compiled from two clinical trials. Participants (N = 54) were adolescents and young adults ages 15-24 who reported consuming alcohol at least twice per week, expressed interest in reducing alcohol use, and reported lifetime cannabis use. Participants provided laboratory and daily-life smartphone report data prior to randomization to treatment conditions in the parent trials. Mixed-effect models tested a priori hypotheses, which received mixed support. Cannabis craving was not heightened following alcohol-cue presentation in the laboratory but was elevated in daily life when alcohol cues were visible. The effect of laboratory alcohol cues was moderated by cannabis use frequency, with higher frequencies associated with greater cannabis craving, while the effect of daily-life alcohol cues on cannabis craving was not moderated by cannabis use frequency. Finally, alcohol cue-induced cannabis craving in the laboratory was associated with greater daily-life cannabis craving, irrespective of the presence of naturalistic alcohol cues. Overall, exposure to alcohol cues in daily life may flag situations with increased risk of cannabis craving, supporting the idea of cross cue reactivity and implicating naturalistic alcohol cues as an intervention target for individuals who co-use alcohol and cannabis. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

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

The effect of alcohol use on smoking cessation: A systematic review.

Only a small minority of all attempts to stop smoking is successful, especially among smokers who are heavy drinkers and those with an alcohol use disorder. The current systematic review focusses on the negative effects of alcohol use, either before or during attempts to quit smoking, on the success rate of these attempt(s) in alcohol drinking tobacco smokers. We conducted a systematic review of naturalistic and experimental studies, which included at least 40 tobacco smokers with a recorded drinking status (non-drinking, heavy drinking, alcohol use disorder) and a clearly documented change in alcohol consumption. We could not conduct a meta-analyses and, thus, used consistency across studies to draw conclusions. The evidence presented here shows that alcohol use is associated with lower rates of success in quitting smoking in 20 out of 27 studies. This includes both lapses and relapses. Similarly, in 19 out of 20 long-term follow-up studies, the duration of smoking abstinence was shorter among persons with higher alcohol consumption. Finally, 12 out of 13 experimental studies showed that exposure of smokers to alcohol cues or to drinking of alcohol, induce a strong propensity to smoke. It is, therefore, recommended for smokers who drink alcohol and who intend to quit smoking to use an integrated approach i.e., to stop or substantial reduce their alcohol consumption before and/or during their attempt to quit smoking.

Cue exposure for alcohol use disorders: A commentary on Kiyak et al. (2023)

While cue exposure therapy (CET) gives similar effects to cognitive-behavior therapies (CBTs) for Alcohol Use Disorder, it does not consistently add to effects of CBT alone. If the non-random trial of Nattala, Murthy, Leung, Rentala and Ramakrishna (2018) is omitted from the systematic review and meta-analysis of Kiyak, Simonetti, Norton and Deluca (2023), even average effects against less stringent controls are not substantial. Some trials have used sub-optimal versions of CET, but effects of CET are also constrained by the fact that many alcohol dependent patients do not exhibit strong craving. In vivo coping skills practice in the presence of powerful alcohol cues remains a viable treatment, especially if a key focus is on skills with wide situational application rather than solely on habituation. Multisensory motivational imagery for alcohol control represents one such strategy.