Lara A. Ray’s research while affiliated with University of California, Los Angeles and other places

The present study examined the association of mood states, alcohol cue exposure, and their synergistic effect on alcohol consumption and subjective craving during early abstinence. A community sample of 50 (24 females, average age 41.68 years old) individuals with current alcohol use disorder and an intrinsic motivation to reduce/quit alcohol use completed a quit attempt and daily diary assessments (DDAs). Electronic DDAs asked about previous-day drinking, alcohol craving, mood states, and exposure to alcohol cues. Analyses using mixed models tested the main effects and synergistic effects of mood states and alcohol cue exposure on alcohol consumption and subjective craving during the quit attempt. Daily negative mood was associated with same-day alcohol craving (b = 0.18, p = .01), in that higher ratings of negative mood were associated with greater alcohol craving. Daily negative mood was associated with same-day number of drinks consumed (b = 0.35, p < .0001), such that higher negative mood was associated with higher alcohol consumption. Alcohol cue exposure predicted next-day alcohol craving (b = 0.26, p = .02), such that higher cue exposure predicted greater next-day craving for alcohol. Findings underscore the role of negative mood states and exposure to alcohol cues on alcohol consumption and craving during a quit attempt. These findings suggest that negative mood states and alcohol-related cues may be useful targets for just-in-time interventions.

Rationale Two prominent neurobiological models of addiction, the allostatic and incentive-sensitization models, have guided clinical research on alcohol use disorder (AUD). While these models are often viewed in isolation, it is plausible these theories are complimentary. Objectives Use naturalistic, daily diary reports to determine whether positive and negative mood states influence alcohol cue sensitivity in a clinical sample with AUD. Methods This is an exploratory analysis of daily diary data collected from a non-treatment seeking sample with current AUD over two weeks. Eligible adult participants (N = 50) were enrolled in a medication trial for AUD. Each morning, participants retrospectively reported on pre-drinking mood states, alcohol cue exposure, and craving levels, and subsequent alcohol intake occurring the previous day. Multilevel models tested the singular and interactive relationships between cue exposure and mood states with craving and drinking. Within-person and between-person outcomes were assessed. Exploratory analyses examined whether individuals with withdrawal-related dysphoria were more vulnerable to mood states and cue-reactivity. Results Greater cue exposure was associated with higher daily drinking levels (p = .001), but not daily alcohol craving. Higher negative mood (p < .0001) and lower positive mood (p = .012) were associated with higher daily alcohol craving, but not same-day drinking. As negative mood levels increased (p < .01) and positive mood levels decreased (p = .010), the relationship between cue exposure and same-day drinking became stronger. These findings were most pronounced among those with withdrawal-related dysphoria. Conclusions Findings provided concomitant support for the allostatic model and incentive-sensitization model as determinants of alcohol craving and drinking among individuals with AUD.

Background: There has been a dramatic rise in alcohol consumption and alcohol use disorder (AUD) among women. Recently, the field has made substantial progress toward better understanding sex and gender differences in AUD. This research has suggested accelerated progression to AUD and associated health consequences in women, a phenomenon referred to as "telescoping."Objective: To examine evidence for the telescoping hypothesis from a biopsychosocial perspective.Methods: This narrative review examined and integrated research on biological, psychological, and socio-environmental factors that may contribute to the development and progression of AUD in women.Results: Biopsychosocial research has revealed sex- and gender-specific risk factors and pathways to AUD onset and progression. Biological sex differences render females more vulnerable to alcohol-related toxicity across various biological systems, including the brain. Notably, sex and gender differences are consistently observed in the neural circuitry underlying emotional and stress regulation, and are hypothesized to increase risk for an internalizing pathway to AUD in women. Psychological research indicates women experience greater negative emotionality and are more likely to use alcohol as a means to alleviate negative emotions compared with men. Socio-environmental factors, such as familial and peer isolation, appear to interact with biological and psychological processes in a way that increases risk for negative emotionality and associated alcohol use in women.Conclusion: There appears to be a complex interplay of biopsychosocial factors that increase risk for AUD onset and progression in women through an internalizing pathway. Developing targeted interventions for women with AUD that specifically target internalizing processes is critical.

Background The γ‐aminobutyric acid‐B (GABAB) receptor is a promising target for the development of new medications to treat alcohol use disorder (AUD). The GABAB agonist baclofen has been reported to reduce alcohol consumption but is associated with some undesirable side effects, including sedation. ASP8062 is a novel compound that acts as a positive allosteric modulator at the GABAB receptor and may be more tolerable than baclofen. This proof‐of‐concept human laboratory clinical trial evaluated the safety profile of ASP8062 and tested its effects on cue‐elicited alcohol craving and alcohol use among treatment‐seeking individuals with AUD. Methods This double‐blind, randomized, multisite trial tested the effect of ASP8062 (25 mg once daily), relative to placebo, on alcohol cue‐elicited craving in a laboratory setting and alcohol consumption, craving, mood, sleep, cigarette smoking, and alcohol‐related consequences in the natural environment over a 6‐week treatment period. Participants were 60 individuals (26 females and 34 males) with moderate or severe AUD. Results ASP8062, relative to placebo, was well tolerated, and there were no adverse events (AEs) that significantly differed between treatment groups. Most AEs were mild/moderate, and there were no serious AEs among individuals treated with ASP8062. However, ASP8062 did not attenuate alcohol cue‐elicited craving compared with placebo. Moreover, exploratory analyses indicated that ASP8062, relative to placebo, did not significantly affect alcohol consumption, naturalistic alcohol craving, mood, sleep, cigarette smoking, or alcohol‐related negative consequences during the 6‐week treatment period. Conclusions Although ASP8062 was well tolerated with no serious AEs, the novel compound did not significantly dampen alcohol cue‐elicited craving or improve other AUD‐related outcome measures. These data indicate positive allosteric modulation of the GABAB receptor at the dose evaluated here may not blunt alcohol cue‐elicited craving, and preliminary drinking outcome data suggest it may not be an efficacious treatment strategy for AUD.

Background Insomnia commonly co‐occurs with alcohol use disorder (AUD) and predicts poorer outcomes for those with AUD. Insomnia and AUD are individually associated with increases in systemic inflammation. Insomnia and inflammation both serve as risk factors for relapse in AUD. However, little is known about the relationship between insomnia and systemic inflammation in individuals with AUD. Therefore, the present study examined the relationship between the severity of insomnia symptoms and plasma levels of inflammatory cytokines in a sample of treatment‐seeking individuals with an AUD. Methods This secondary analysis included 101 (61M/40F) individuals with an AUD. Participants were categorized into groups based on their scores on the Insomnia Severity Index: no insomnia (n = 47), subthreshold insomnia (n = 37), and clinical insomnia (n = 17). Participants provided blood samples to measure plasma levels of four peripheral markers of inflammation (IL‐6, IL‐8, TNF‐α, and CRP). Inflammatory marker levels were compared between groups. Interactive effects of sex and AUD severity were examined. Results There was a significant main effect of insomnia group on log IL‐8 levels (F = 6.52, p = 0.002), such that individuals with AUD and clinical insomnia had higher log IL‐8 levels compared to both the no insomnia and subthreshold insomnia groups (ps ≤ 0.05). Sex and AUD severity interacted with this relationship, such that men with clinical insomnia and AUD and individuals with severe AUD had higher log IL‐8 levels. There were no significant effects of insomnia on IL‐6, TNF‐α, or CRP levels. Conclusion The present study identified a specific elevation in IL‐8 levels in individuals with an AUD and clinical insomnia that was not identified in other markers of peripheral inflammation (IL‐6, TNF‐α, CRP). Sex and AUD severity interacted with insomnia symptoms, indicating that those with clinical insomnia and severe AUD or male sex may be the most vulnerable to the inflammatory consequences associated with AUD and clinical insomnia symptoms.