Food Cue Reactivity Meets the Reinforcer Pathology Model: Behavioral Economic Measures of Cue-Induced Changes in Food Reinforcer Efficacy.

Food cue reactivity, or behavioral sensitivity to conditioned food cues, is an eating pattern observed in those with obesity and binge-eating disorder. The reinforcer pathology model, which characterizes overconsumption of a reinforcer such as food may be relevant to food cue reactivity, especially in those with obesity and binge-eating disorder. The reinforcer pathology model posits that steep delay discounting (DD) and demand elasticity are processes involved in the overconsumption of food. Two of our recent studies examine the extent to which reactivity to conditioned food cues may be involved in food reinforcer pathologies. First, food cues were conditioned with Oreo cookies with binge-eating prone (BEP) and binge-eating resistant (BER) rats. Delay discounting was compared before and after conditioning. Food cues induced steeper DD for rats, though BEP rats showed some evidence for greater sensitivity to this effect than BER rats, albeit this difference was not significant. Second, healthy-weight humans and humans with overweight/obese BMI underwent conditioning of visual cues paired with M&M candies. After acquisition, cues induced greater demand intensity and inelasticity for food compared to baseline. Participants with overweight/obese BMI, compared to controls, also showed some evidence for greater sensitivity to this change ininelasticity compared to healthy-weight participants, but this difference was also not significant. Food cues, then, may induce changes in DD and economic demand, supporting the relevance of reinforcer pathologies.

The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.

N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.

A cue reactivity experiment: Exposure to images of alcoholic beverages and social contexts on alcohol cravings, motivations, attitudes, approval, and behavior.

The incentive-sensitization theory of addiction postulates that relevant cues can trigger alcohol cravings, tendencies, and related outcomes. Additionally, consistent with the encoding specificity principle and social impact theory, social contexts depicting people can activate pro-alcohol reactions and tendencies. This randomized experiment tested the cue reactivity effects of exposure to images depicting variations in the number of people consuming alcoholic or nonalcoholic beverages on alcohol-related cravings and outcomes. The sample consisted of 594 adult alcohol users who passed manipulation checks. Participants were randomly assigned to a condition in a 2 (beverage type cue manipulation: alcoholic vs. nonalcoholic) × 3 (social context cue manipulation: beverage-only [no people] vs. solitary drinking [1 person] vs. social drinking [2 or more people]) factorial design and primed with a series of photographs. Dependent variables measured alcohol cravings, alcohol motives, alcohol attitudes, alcohol approval, and alcohol behavior. Factorial MANCOVA and ANCOVAs were performed. Main effects for the social context manipulation were found. Specifically, the social drinking condition compared to the beverage-only condition induced significantly higher pro-alcohol cravings, attitudes, and behaviors. The beverage type manipulation did not influence the dependent variables. The findings offer insights that visual cues depicting social drinking scenarios activated alcohol-related cravings and outcomes, regardless of whether the beverages shown were alcoholic or nonalcoholic. This priming experiment helps to understand the social mechanisms underlying cue reactivity and offers implications for advancing cue-based alcohol interventions.

Changes of attentional bias in patients with alcohol use disorder during abstinence: A longitudinal study.

BACKGROUND: Alcohol Use Disorder (AUD) is linked to an attentional bias towards alcohol-related cues (e.g. images, smells), which acquire incentive properties and promote continued consumption. METHOD: We investigated how the general and alcohol attentional bias evolved longitudinally in AUD patients along two periods of abstinence: t = 0 (baseline, 1-3 months of abstinence) and t = 1 (follow-up; 6 months of abstinence), as well as their relationship with alcohol-related variables. General and alcohol-specific attentional bias were evaluated by the Classic and the Alcohol Stroop tests (neutral and alcohol conditions) in abstinent AUD patients and controls. RESULTS: At t = 0, the AUD group exhibited both general and alcohol-specific attentional biases, with greater effect in the general bias. At t = 1, alcohol-specific attentional bias decreased specifically in the AUD group and reached control levels (with interference index levels increasing from 1-3 months to 6 months). However, general attentional bias showed a trend toward improvement but it did not significantly change through abstinence process (linear mixed models, controlling for age, BMI, sex and education). CONCLUSIONS: In AUD patients, general and alcohol attentional biases exhibit different trajectories during abstinence, with the attentional bias toward alcohol improving significantly throughout this process whereas general attentional bias is maintained.

Virtual Reality Environmental Enrichment Effects on Craving for Cigarette in Smokers.

Background: Preclinical studies suggested the exposure to environmental enrichment (EE) as an intervention able to prevent or reduce nicotine-taking and nicotine-seeking behaviors. Virtual reality (VR) may help to test the effects of EE in smokers in a reproducible and feasible manner. Materials and Methods: In the present study, 31 smokers (14 women) were divided into two groups: (1) exposure to a virtual EE (VR-EE) and (2) exposure to a virtual neutral environment (VR-NoEE). Cigarette craving was assessed as basal and evoked, at different timepoints during the session. Behavior activity during VR exposure, mood, and subjective measures were also collected. Results: EE exposure in VR significantly reduced craving scores from basal timepoint. This was not observed in the VR-NoEE group, which significantly increased craving compared with values at neutral scenario. When both groups were exposed to smoking-related VR scenario, the VR-EE group showed an increased craving compared with previous timepoint up to score values not different from those in the VR-NoEE group. A significant positive correlation between basal craving scores and interactive behavior with virtual smoking cues was observed in the VR-NoEE but not in the VR-EE group. Conclusion: These findings suggest that virtual EE might have an inhibitory effect in smokers on basal, but not on evoked cigarette craving. Noteworthily, the interactive activity correlation to craving scores in the VR-NoEE participants was not observed in the VR-EE group, adding further evidence that the enrichment simulation was nonetheless able to modify behavior in the smoking-related scenario.

Behaviourally assessed negative urgency is uniquely associated with binge-eating frequency.

OBJECTIVE: Binge eating appears to be associated with impulsivity, especially in response to negative affect (i.e., negative urgency). However, negative urgency is typically assessed via self-report, which captures only some aspects of urgency and may be subject to bias. Few studies have examined impulsivity following experimental manipulations of affect in binge-eating samples. METHOD: In the present study, individuals who engage in regular binge eating completed a behavioural impulsivity (go/no-go) task with high- and low-calorie food stimuli, once following negative affect induction and once following neutral affect induction. RESULTS: Greater behavioural impulsivity to high-calorie food cues while in a negative (and not a neutral) affective state was associated with more frequent binge-eating behaviour. Further, this behavioural measure of negative urgency uniquely accounted for variance in binge-eating frequency when controlling for self-reported negative urgency, suggesting that behavioural measures may be a useful complement to self-report measures. DISCUSSION: These findings provide novel and compelling evidence for the relationship between negative urgency and binge eating, highlighting negative urgency as a potentially important target for intervention.

Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial.

BACKGROUND: Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options. METHODS: This preliminary study examined the effect of N-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6-19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of N-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after N-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving. RESULTS: In the full sample (n = 31), there was no effect of N-acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ s = 0.00-0.07) or self-reported acute alcohol craving (p = 0.18, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.06). However, N-acetylcysteine did reduce self-reported generalized alcohol craving (p = 0.03, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (n = 19), results remained unchanged. CONCLUSIONS: N-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.

Correspondence between the alcohol-P3 event-related potential and alcohol reward phenotypes among young adults.

BACKGROUND: Behavioral economic theory suggests that the value of alcohol depends upon elements of the choice context, such that increasing constraints on alternatives (e.g., price) or increasing the benefits of alcohol (e.g., social context) may result in greater likelihood of heavy drinking. The P3 event-related potential elicited by alcohol-related cues, a proposed marker of incentive salience, may be an electrophysiological parallel for behavioral economic alcohol demand. However, these indices have not been connected in prior research, and studies typically do not disaggregate social influences in the context of alcohol cue reactivity. METHOD: The current study recruited heavy drinking young adults (N = 81) who completed measures of alcohol use and alcohol demand, in addition to a 2 (social/nonsocial) × 2 (alcohol/nonalcohol) visual oddball task to elicit the P3. RESULTS: In multilevel models controlling for demographic characteristics, P3 reactivity was greater to alcohol (p < 0.001) and social (p < 0.001) cues than to nonalcohol and nonsocial cues, but without a significant interaction. Higher alcohol consumption (p = 0.02) and lower elasticity of demand (p = 0.01) were associated with greater P3 response to alcohol than nonalcohol cues. CONCLUSIONS: The results highlight a brain-behavior connection that may be an important marker for alcohol reward across units of analysis and may be sensitive to changes in the economic choice contexts that influence the likelihood of alcohol use.

Neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence.

AIMS: Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. METHODS: Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. RESULTS: Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. CONCLUSIONS: The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.

Validation of a laboratory craving assessment and evaluation of 4 different interventions on cravings among adults with overweight or obesity.

Food cue reactivity (FCR) is an appetitive trait associated with overeating and weight gain. We developed a laboratory craving assessment to objectively evaluate cognitive aspects of FCR. This study examined the preliminary construct and criterion validity of this craving assessment and evaluated 4 different interventions, 2 of which incorporated cue-exposure treatment for food, on craving over treatment and follow-up. 271 treatment-seeking adults with overweight/obesity (body mass index = 34.6[5.2]; age = 46.5[11.8]; 81.2% female; 61.6% non-Latinx White) completed the Food Cue Responsivity Scale and the laboratory craving assessment, during which they alternated holding and smelling a highly craved food and provided craving ratings over 5 min. Participants were subsequently randomized to 26 treatment sessions over 12-months of ROC, Behavioral Weight Loss (BWL), a combined arm (ROC+) and an active comparator (AC), and repeated the craving assessment at post-treatment and 12-month follow-up. Linear mixed-effects models assessed associations between trial type (holding vs. smelling), trial number, pre-treatment FCR, treatment arm, assessment time point, and craving. Cravings were greater when smelling vs. holding food (b = 0.31, p < 0.001), and cravings decreased over time (b = -0.02, p < 0.001). Participants with higher pre-treatment FCR reported elevated cravings (b = 0.29, p < 0.001). Longitudinally, we observed a significant 3-way interaction in which treatment arm modified the relationship between pre-treatment FCR and craving over time (F(17,5122) = 6.88, p < 0.001). An attenuated FCR-craving relationship was observed in ROC+ and BWL from baseline to post-treatment but was only sustained in BWL at follow-up. This attenuation was also observed in ROC and AC from post-treatment to follow-up. The preliminary validity of this laboratory craving assessment was supported; however, greater craving reductions over time in ROC/ROC+ compared to BWL and AC were not consistently observed, and thus do not appear to fully account for the moderating effect of FCR on weight losses observed in the trial.

Sex-Dependent Differences in the Neural Correlates of Cocaine and Emotional Cue-Reactivity in Regular Cocaine Users and Non-Drug-Using Controls: Understanding the Role of Duration and Severity of Use.

INTRODUCTION: The development of cocaine use disorder in females is suggested to be more strongly related to neural mechanisms underlying stress-reactivity, whereas in males it is suggested to be more strongly related to neural mechanisms underlying drug cue-reactivity. Existing evidence, however, is based on neuroimaging studies that either lack a control group and/or have very small sample sizes that do not allow to investigate sex differences. METHODS: The main objective of the current study was to investigate sex differences in the neural correlates of cocaine and negative emotional cue-reactivity within high-risk intranasal cocaine users (CUs: 31 males and 26 females) and non-cocaine-using controls (non-CUs: 28 males and 26 females). A region of interest (ROI) analysis was applied to test for the main and interaction effects of group, sex, and stimulus type (cocaine cues vs. neutral cocaine cues and negative emotional cues vs. neutral emotional cues) on activity in the dorsal striatum, ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC). RESULTS: There were no significant sex or group differences in cocaine cue-reactivity in any of the ROIs. Results did reveal significant emotional cue-reactivity in the amygdala and VS, but these effects were not moderated by group or sex. Exploratory analyses demonstrated that emotional cue-induced activation of the dACC and VS was negatively associated with years of regular cocaine use in female CUs, while this relationship was absent in male CUs. CONCLUSIONS: While speculative, the sex-specific associations between years of regular use and emotional cue-reactivity in the dACC and VS suggest that, with longer years of use, female CUs become less sensitive to aversive stimuli, including the negative consequences of cocaine use, which could account for the observed "telescoping effect" in female CUs.

Cue-Reactive Phenomenology Mediates the Relationship Between Positive Schizotypy and Cue-Reactive Urge to Gamble in Poker-Machine Gamblers.

Although ubiquitous in numerous nightlife cultures, poker-machines present a high risk for problematic use and addiction. Previous research has demonstrated that gambling cues (e.g., flashing lights) can activate gambling urges in poker-machine gamblers. However, the processes that contribute to the maintenance of cue-reactive urges to gamble remain unclear. Consequently, the present study explored whether positive schizotypy predicted gambling urge, and whether cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. Seventy adults aged between 19 and 68 (M = 48.86, SD = 12.82) participated in an online cue-reactivity experiment. Participants first completed the Problem Gambling Severity Index and the Unusual Experiences subscale of the Short Oxford-Liverpool Inventory of Feelings and Experiences. Subsequently, at three time points (i.e., baseline, directly after a neutral cue, and directly after a gambling cue) participants completed the Altered State of Awareness, Altered Time Sense, and Absorption subscales of the Phenomenology of Consciousness Inventory and a visual analogue scale measuring cue-reactive urge to gamble. It was found that positive schizotypy was significantly positively correlated with cue-reactive urge to gamble. Additionally, cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. The theoretical, clinical and practical implications are discussed.

Effects of Trauma Cue Exposure and Posttraumatic Stress Disorder (PTSD) on Affect and Cannabis Craving in Cannabis Users With Trauma Histories: Use of Expressive Writing as an Online Cue-Reactivity Paradigm: Effets de l'exposition aux signaux traumatiques et du SSPT sur l'affect et le besoin de cannabis chez les consommateurs de cannabis ayant des antécédents de traumatismes : utilisation de l'écriture expressive comme paradigme de réactivité en ligne.

OBJECTIVES: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) commonly co-occur. Conditioned associations between psychological trauma cues, distress, cannabis use, and desired relief outcomes may contribute to the comorbidity. These conditioned associations can be studied experimentally by manipulating trauma cue exposure in a cue-reactivity paradigm (CRP) and examining effects on affective and cognitive outcomes in participants with and without PTSD. However, traditional CRPs take place in-lab limiting recruitment/power. We aimed to examine the effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on affective and craving outcomes using a stand-alone online expressive writing CRP. METHODS: Participants (n = 202; 43.6% male; Mage = 42.94 years, SD = 14.71) with psychological trauma histories and past-month cannabis use completed a measure of PTSD symptoms (PTSD Checklist-5 for DSM-5 [PCL-5]) and were randomized to complete either a trauma or neutral expressive writing task. Then they completed validated measures of affect (Positive and Negative Affect Schedule-Short Form [PANAS-SF]) and cannabis craving (Marijuana Craving Questionnaire-Short Form [MCQ-SF]). RESULTS: Linear mixed models tested the hypothesized main and interactive effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on negative and positive affect (PANAS-SF) and cannabis craving dimensions (MCQ-SF). The hypothesized main effects of trauma versus neutral expressive writing were found for negative affect and the expectancy dimension of cannabis craving and of PTSD group for negative affect and all cannabis craving dimensions; no interactions were observed. CONCLUSIONS: Expressive writing appears a useful online CRP. Interventions focused on reducing negative affect and expectancy craving to trauma cues may prevent/treat CUD among cannabis users with PTSD. PLAIN LANGUAGE SUMMARY TITLE: The Use of an Online Expressive Writing as a Trauma Cue Exposure: Effects on Craving and Emotions.

People who have gone through trauma sometimes experience both post-traumatic stress disorder (PTSD) and a tendency to use cannabis excessively (cannabis use disorder or CUD). Researchers believe that there's a connection between traumatic memories, emotional distress, cannabis use, and the relief people feel afterward. These associations can be studied experimentally by using a cue-reactivity paradigm (CRP) to examine effects on craving and affective outcomes in those with and without PTSD. This study included 202 participants who had a history of trauma and reported regular cannabis use. They were randomly assigned to write about a traumatic or neutral personal experience. After, they filled out questionnaires about their PTSD symptoms, emotions (both positive and negative), and cravings for cannabis during the task. We expected that the type of writing task (those assigned to the trauma vs. neutral condition) and PTSD status would be associated with increased cannabis craving, negative emotions, and reduced positive emotions. We found that writing about trauma increased negative feelings and positive expectations about using cannabis for relief, especially for those with PTSD. People with PTSD also seemed to have more ongoing negative feelings and cravings for cannabis. The authors suggest that traditional in-lab experiments might be necessary to fully understand how trauma reminders can influence cravings and emotions in individuals with PTSD-CUD.

Neural Correlates of Stress and Alcohol Cue-Induced Alcohol Craving and of Future Heavy Drinking: Evidence of Sex Differences.

OBJECTIVE: Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue-induced craving compared with neutral cue-induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences. METHODS: Treatment-seeking adults with AUD (N=77; 46 men and 31 women) completed a functional MRI task involving stress, alcohol, and neutral cue exposure with repeated assessments of alcohol craving. Most of these participants (N=72; 43 men and 29 women) then participated in an 8-week standardized behavioral AUD treatment program, during which the percentage of heavy drinking days was assessed. RESULTS: Significant increases in both stress and alcohol cue-induced craving relative to neutral cue-induced craving were observed, with a greater alcohol-neutral contrast in craving relative to the stress-neutral contrast among men and equivalent stress-neutral and alcohol-neutral contrasts in craving among women. Whole-brain voxel-based regression analyses showed craving-associated hyperactivation in the neutral condition, but hypoactive prefrontal (ventromedial and lateral prefrontal, supplementary motor, and anterior cingulate regions) and striatal responses during exposure to stressful images (stress-neutral contrast) and alcohol cues (alcohol-neutral contrast), with significant sex differences. Additionally, a higher percentage of heavy drinking days was associated with hypoactivation of the subgenual anterior cingulate cortex and the bed nucleus of the stria terminalis in the stress-neutral contrast among women, hyperactivation of the hypothalamus in the stress-neutral contrast among men, and hyperactivation of the hippocampus in the alcohol-neutral contrast among men. CONCLUSIONS: Sex differences in stress- and alcohol cue-induced responses in the cortico-striatal-limbic network related to subjective alcohol craving and to heavy drinking indicated that distinct brain circuits underlie alcohol use outcomes in women and men. These findings underscore the need for sex-specific therapeutics to address this neural dysfunction effectively.

Towards virtual reality exposure therapy for cocaine use disorder: A feasibility study of inducing cocaine craving through virtual reality.

Background: Craving is a core symptom of cocaine use disorders (CUD). Inducing craving in exposure to substance cues is of relevant interest for numerous clinical applications. Virtual reality exposure (VRE) might be a promising candidate for improving cue-exposure paradigms but remains almost not studied for cocaine. This feasibility study's main aim is to assess whether VRE to cocaine cues is capable to induce cocaine craving compared with VRE to neutral cues. Methods: We conducted a within-subjects controlled trial in which cocaine users performed 3 consecutive 10 mins-tasks: VRE to neutral and cocaine cues, and a relaxation-based resting procedure. The primary outcome was the change in Cocaine Craving Questionnaire-Brief (CCQ-Brief) scores between VRE to neutral and cocaine cues. Secondary outcomes included between-tasks changes in scores of cocaine craving, pleasant/unpleasant emotions as well as self-efficacy to cope with craving. Results: We recruited 11 chronic cocaine users including mostly crack smokers (45 %), cocaine snorters (36 %) and injectors (18 %), with 73 % of participants meeting DSM-IV criteria for cocaine dependence and/or abuse. Non-parametrical sign tests indicated significant large increases of CCQ-Brief scores from neutral to cocaine cue-VRE (S(11) = 11, p < 0.01, Cliff's Δ = 0.65, 95 % CI: 0.17-0.88). Exploratory comparative analyses indicated significant changes after our post-cues VRE relaxation procedure, with cocaine craving and emotions restored to baseline. Conclusions: VRE to cocaine cues was feasible and capable to induce cocaine craving in cocaine users. This second VRE-based cue-reactivity study in cocaine paves the way for unexplored research on VRE clinical applications for CUD.

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

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

Biological sex and hormonal contraceptive associations with drug cue reactivity in cannabis use disorder.

Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

Characterizing alcohol cue reactive and non-reactive individuals with alcohol use disorder.

PURPOSE: Exposure to alcohol-related cues is thought to elicit a conditional response characterized by increased craving in individuals with alcohol use disorder (AUD). In the context of AUD research, it is important to consider that not all individuals with an AUD are alcohol cue reactive. This study systematically examined subjective alcohol cue reactivity and its clinical and drinking correlates in individuals with an AUD enrolled in a human laboratory pharmacotherapy trial. METHODS: Individuals with current moderate-to-severe AUD (N = 52) completed a standard alcohol cue exposure paradigm and individual difference assessments as part of a human laboratory pharmacotherapy trial (NCT04249882). We classified participants as cue reactive (CR+) and cue non-reactive (CR-), as indicated by self-reported, subjective alcohol urge, and examined group differences in baseline clinical characteristics and drinking outcomes over the course of the trial. RESULTS: Twenty participants (38%) were identified as CR+, while 32 participants (62%) were identified as CR-. The CR+ and CR- groups did not differ in baseline drinking and AUD clinical characteristics, but the groups differed in race composition (p = 0.02) and smoking prevalence (p = 0.04) such that the CR+ group had lower prevalence of smokers. The CR+, compared with the CR-, group drank more during the trial titration period (p = 0.03). Both groups reduced drinking across the trial (p's < 0.001), but the CR+ group exhibited a smaller reduction in drinking, compared with the CR- group (time x group, p = 0.029; CR-, p < 0.0001; CR+: p = 0.01). CONCLUSION: Results indicate that cue reactivity is a heterogenous construct. Recognizing this heterogeneity, and the clinical factors associated with it, is critical to advancing this paradigm as an early efficacy marker in AUD research.

Neural responses to gaming content on social media in young adults.

Excessive gaming can impair both mental and physical health, drawing widespread public and clinical attention, especially among young generations. People are now more exposed to gaming-related content on social media than before, and this exposure may have a significant impact on their behavior. However, the neural mechanisms underlying this effect remain unexplored. Using functional magnetic resonance imaging (fMRI), this study aimed to investigate the neural activity induced by gaming-related content on social media among young adults casually playing online games. While being assessed by fMRI, the participants watched gaming-related videos and neutral (nongaming) videos on social media. The gaming-related cues significantly activated several brain areas, including the medial prefrontal cortex, posterior cingulate cortex, hippocampus, thalamus, superior/middle temporal gyrus, precuneus and occipital regions, compared with the neutral cues. Additionally, the participants' gaming desire levels positively correlated with a gaming-related cue-induced activation in the left orbitofrontal cortex and the right superior temporal gyrus. These findings extend previous studies on gaming cues and provide useful information to elucidate the effects of gaming-related content on social media in young adults. Continued research using real-world gaming cues may help improve our understanding of promoting gaming habits and provide support to individuals vulnerable to gaming addiction.

The effects of a retrieval cue on renewal of conditioned responses in human appetitive conditioning.

Contextual renewal of reward anticipation may be one potential mechanism underlying relapse in eating and substance use disorders. We therefore tested retrieval cues, a method derived from an inhibitory retrieval-based model of extinction learning to attenuate contextual renewal using an appetitive conditioning paradigm. A pilot study was carried out in Experiment 1 to validate a differential chocolate conditioning paradigm, in which a specific tray was set up as a conditioned stimulus (CS) for eating chocolate (unconditioned stimulus, US). Using an ABA renewal design in Experiment 2, half of the participants were presented with a retrieval cue in the acquisition phase (group AC) and the other half in the extinction phase (group EC). Presentation of the retrieval cue in the EC was associated with reduced renewal of US-expectancy, while there was a clear renewal effect for US-expectancy in the AC. One limitation was the difference in cue presentations between both groups due to the number of trials in acquisition and extinction. Experiment 3 therefore aimed at replicating the results of Experiment 2, but with fewer cue presentations for the EC to match the AC. No significant group differences were observed indicating no effect of the retrieval cue. Theoretical and clinical implications in light of the differing results are discussed.