Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Neuroimaging studies of cannabidiol and potential neurobiological mechanisms relevant for alcohol use disorders: a systematic review.

The underlying neurobiological mechanisms of cannabidiol's (CBD) management of alcohol use disorder (AUD) remains elusive.Aim We conducted a systematic review of neuroimaging literature investigating the effects of CBD on the brain in healthy participants. We then theorise the potential neurobiological mechanisms by which CBD may ameliorate various symptoms of AUD.Methods This review was conducted according to the PRISMA guidelines. Terms relating to CBD and neuroimaging were used to search original clinical research published in peer-reviewed journals.Results Of 767 studies identified by our search strategy, 16 studies satisfied our eligibility criteria. The results suggest that CBD modulates γ-Aminobutyric acid and glutamate signaling in the basal ganglia and dorso-medial prefrontal cortex. Furthermore, CBD regulates activity in regions associated with mesocorticolimbic reward pathways; salience, limbic and fronto-striatal networks which are implicated in reward anticipation; emotion regulation; salience processing; and executive functioning.Conclusion CBD appears to modulate neurotransmitter systems and functional connections in brain regions implicated in AUD, suggesting CBD may be used to manage AUD symptomatology.

Economic evaluations of alcohol pharmacotherapy: Systematic review of economic evaluations of pharmacotherapy for the treatment of alcohol use disorder.

OBJECTIVE: Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies. METHODS: A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality. RESULTS: A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%. CONCLUSION: Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.

N acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial.

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F = 9.18, P < 0.001), no significant effect of treatment (F = 0.75, P = 0.79), and a significant time x treatment (NAC vs PL) effect (F = 2.73, P < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F = 3.16, P < 0.05) but no significant effect of treatment or time x treatment (P = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy.

Central markers of neuroinflammation in alcohol use disorder: A meta-analysis of neuroimaging, cerebral spinal fluid, and postmortem studies.

INTRODUCTION AND AIMS: There is emerging evidence that heavy long-term alcohol consumption may alter the neuroimmune profile. We conducted a meta-analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. DESIGN AND METHODS: A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for AUD-related terms in combination with neuroinflammatory markers and cytokine- and chemokine-related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on postmortem and PET studies. RESULTS: Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (𝑄 (14) = 62.02, 𝑝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (𝑑 = 1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11 C] PBR28 total volume of distribution (V T ) for translocator protein in the hippocampus (g = -1.95 [95% CI -2.72, -1.18], p < 0.001) of the alcohol group compared to controls. CONCLUSION: There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain.

Impaired Decision-Making and Skin Conductance Responses Are Associated with Reward and Punishment Sensitivity in Individuals with Severe Alcohol Use Disorder.

INTRODUCTION: Individuals with alcohol use disorder (AUD) have difficulties regulating alcohol consumption, despite adverse drinking-related consequences. This may be due to incapacity incorporating previous negative feedback from drinking, resulting in impaired decision-making. METHODS: We assessed whether decision-making is impaired in participants with AUD related to severity of AUD, indexed by severe negative drinking consequences using the Drinkers Inventory of Consequences (DrInC) and reward and punishment sensitivity with the Behavioural Inhibition System Behavioural Activation System (BIS BAS) scales. 36 treatment-seeking alcohol-dependent participants completed the Iowa gambling task (IGT) with skin conductance responses (SCRs) measured continuously as an index of somatic autonomic arousal to evaluate impaired expectancy of negative outcomes. RESULTS: Two-thirds of the sample showed behavioural impairment during the IGT, with greater AUD severity related to worse performance. BIS moderated IGT performance according to severity of AUD, with increased anticipatory SCRs for those with fewer reported DrInC severe consequences. Participants with more DrInC severe consequences showed IGT deficits and reduced SCRs regardless of BIS scores. BAS-Reward was associated with increased anticipatory SCRs to disadvantageous deck choices among those with lower AUD severity, while SCRs did not differ related to AUD severity for reward outcomes. DISCUSSION: Effective decision-making in the IGT and adaptive somatic responses were moderated by punishment sensitivity contingent on severity of AUD in these drinkers, with impairments in expectancy to negative outcomes from risky choices, including reduced somatic responses, resulting in poor decision-making processes that may help explain impaired drinking and worse drinking-related consequences.

Assessing the validity of the Wechsler Adult Intelligence Scale (WAIS-IV) in predicting completion in a long-term residential rehabilitation for substance use problems.

BACKGROUND: We aimed to examine the predictive validity of the Weschler Adult Intelligence Scale (WAIS-IV) in predicting treatment completion, over and above educational status. METHODS: One hundred and ninety-six (N = 196) individuals from the Odyssey House Residential Rehabilitation Program, NSW, Australia between 2010 and 2016 were administered a structured interview including substance use disorders and the Verbal Comprehension (VCI), Perceptual Reasoning (PRI), Working Memory (WMI), and Processing Speed (PSI) domains of the WAIS-IV. RESULTS: There were significant differences between our clinical sample and the population norm with respect to the proportion below the mean for PSI (z = 12.27, p < .001), VCI (z = 2.33, p < .02) but not for WMI (z = 1.67, p < .10) or PRI (z = -1.76, p < .08). The WAIS-IV subscales did not significantly predict treatment completion (p's > .16) over and above educational status (p < .01). CONCLUSIONS: Our findings suggest that in clients in drug and alcohol rehabilitation settings a combination of skills may be impacted including Verbal Comprehension and Processing Speed. Moreover, our findings also suggest that WAIS-IV subscales do not predict treatment completion in a drug and alcohol residential setting, over and above a brief assessment of educational status.

Geographical variation in implementation of the Pathways to Comorbidity Care program in Australian drug and alcohol services.

AIM: Comorbid drug and alcohol and mental health disorders are highly prevalent. Significant gaps in service provision make this problem particularly difficult to address in regional Australia. The Pathways to Comorbidity Care (PCC) program was designed to improve management of comorbidity by outpatient drug and alcohol clinicians in New South Wales, Australia. This paper uses the Consolidated Framework for Implementation Research (CFIR) to evaluate variations in implementation outcomes across geographically diverse services. METHODS: Twenty clinicians across three drug and alcohol services from metropolitan, outer metropolitan and regional geographic locations were engaged at multiple levels of influence (directors, managers, clinicians) during the implementation of the multimodal PCC training package. The CFIR guided the development of self-report measures and semi-structured interviews evaluating implementation of the PCC training, and disparities in implementation barriers and facilitators were determined. RESULTS: Metropolitan clinicians identified less barriers than regional clinicians on several intervention characteristics (adaptability, complexity, design quality and packaging), as well as outer setting (peer pressure), inner setting (implementation climate, staff incentives, leadership engagement, available resources) and process (planning, opinion leaders, executing) domains. Regional clinicians evaluated the networks and communications construct more favourably. CONCLUSIONS: Specific barriers identified more strongly by regional clinicians included the importance of communication with local clinicians and leadership about the practicalities of incorporating the approach into routine practice (allocation of time, increased accessibility of implementation team). Metropolitan clinicians provided more favourable evaluations of the package design, implementation climate and specific implementation processes such as a clear and informative implementation plan.

The role of impulsivity in the relationship between affect and alcohol consumption in young adults.

BACKGROUND: Theoretical models of alcohol use posit that individuals consume alcohol to ameliorate negative affect or to heighten positive affect. It is important, however, to consider the influence of factors that may determine an individual's tendency to consume excessive amounts of alcohol under positive and negative circumstances. Thus, the current study examined a large sample of young adults to clarify whether positive and negative affect predict total alcohol consumption on drinking days and whether facets of impulsivity moderate these relationships. METHODS: Six-hundred ninety-three young adults (Mage = 19.71 years, SD = 2.04; female = 62.9%) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales at baseline followed by daily measures of positive and negative affect and self-reported alcohol use for 13 days. Generalized linear mixed models were specified to assess the role of pre-consumption affect on total drinks consumed across drinking days and to determine the moderating effect of each BIS/BAS subscale. RESULTS: Participants were significantly more likely to drink in greater quantities on occasions preceded by higher positive affect but not negative affect. While fun-seeking positively predicted total drinks consumed, there were no significant interaction effects between the BIS/BAS subscales and affect on total drinks consumed. CONCLUSIONS: These findings challenge existing affect regulation models and have implications for ecological momentary interventions aimed at addressing hazardous drinking behaviors.

Relationship between clinician-level attributes and implementation outcomes from the Pathways to Comorbidity Care training program.

BACKGROUND: The process of determining the best strategy for increasing the uptake of evidence-based practice might be improved through an understanding of relevant clinician-level factors. The Pathways to Comorbidity Care (PCC) training program (Louie E, et al., J Dual Diagnosis 17:304-12, 2021) aimed to facilitate integrated management of comorbid drug and alcohol and mental disorders amongst drug and alcohol clinicians. We hypothesised that uptake of integrated management of comorbidity following the implementation of the PCC program would be associated with clinician-level: (i) demographics (gender, education, experience), (ii) attitudes (evidence-based practice, therapist manuals, counselling self-efficacy), and (iii) organisational readiness to change. METHODS: Twenty clinicians participated in the 9-month PCC training program. Attitudes towards evidence-based practices and psychotherapist manuals, self-efficacy, and organisational readiness to change, along with demographics, were measured at baseline. At follow-up, change in Comorbidity Practice (CoP) scores related to integrated comorbidity management were obtained using a file audit checklist and categorised into high (at least 60% increase in CoP), medium or low (a decrease of - 20% or less in CoP). Clinician-level characteristics were examined across the implementation categories. RESULTS: There were no significant differences found between implementation groups on sociodemographic variables (p's > 0.30), attitudes to evidence-based practices, attitudes to therapist manuals, and self-efficacy (p's > 0.52). The high implementation group demonstrated significantly higher scores on leadership practices aspect of organisational readiness to change relative to the low and medium implementation group ((F(2, 16) = 3.63, p = 0.05; Cohen's d = .31) but not on the other subscales (p's > 0.07). CONCLUSIONS: Confidence that leadership will play a positive role in the implementation process may improve effectiveness of comorbidity training programs for drug and alcohol clinicians. On the other hand, contrary to our hypothesis, counselling self-efficacy, evidence-based practice attitudes, attitudes towards therapist manuals, gender, education and experience were not distinguishing factors.

A systematic review of the perceptions and attitudes of mental health nurses towards alcohol and other drug use in mental health clients.

Mental and substance use disorders are leading contributing factors for the Australian non-fatal burden of disease. These disorders frequently co-occur in the mental health population, and mental health nurses are the largest group of professionals treating dual diagnosis. A comprehensive understanding of mental health nurses' attitudes and perceptions is required to inform future implementation of dual diagnosis training programs. A systematic literature review of sources derived from electronic databases including Medline, CINAHL, SCOPUS review, and PsychINFO, along with Connected Papers. Selection criteria included a focus on mental health nurses' attitudes towards dual diagnosis of mental illness and substance use. Extracted data was qualitatively synthesized. Of the 5232 articles retrieved initially, 12 were included in the review. Four themes emerged from the synthesis: drug and alcohol use among mental health consumers (seven studies), caring for dual diagnosis consumers (eight studies), role perception (six studies), and treatment optimism (five studies). Salient beliefs included substance use as a self-inflicted choice (71%) or a form of 'self-medication' (29%); a lack of willingness to provide care (75%), or a strong commitment to care (25%); greater comfort with screening and acute medical management rather than ongoing management (83%); and pessimism about treatment effectiveness (100%). Mental health nurses' beliefs and attitudes towards dual diagnosis were often negative, which is likely to result in poor quality care and treatment outcomes. However, the lack of recent studies in this research area indicates the need for up-to-date knowledge that can inform the development of training programs.

Sex as a Potential Moderator for Baclofen Response in the Treatment of Alcohol Dependence.

Background and Aims: Recent studies indicate that sex may moderate the response to baclofen in the treatment of alcohol use disorder (AUD). We conducted a secondary analysis of a double-blind randomized controlled trial, Baclofen in the treatment of Alcohol Liver Disease (BacALD), to examine the moderating role of sex on treatment response to baclofen in reducing alcohol consumption. Methods: Alcohol-dependent patients (n = 104 including 74 men and 30 women) were treated for 12 weeks with baclofen (30 mg/day or 75 mg) or placebo. Predefined primary outcomes included time to lapse (any drinking) and relapse (≥ 5 drinks per day in men and ≥ 4drinks per day in women). Other outcomes included drinks per drinking day, the number of heavy drinking days, and percentage of days abstinent. We also examined the frequency of adverse events with an exploratory dose-response analysis. Results: There was a main effect of baclofen for days to first lapse for women (Log Rank: χ2 = 6.23, p = 0.01, d = 0.49) but not for men (Log Rank: χ2 = 2.48, p = 0.12, d = 0.22) and a marginal effect of baclofen for days to first relapse for women (Log Rank: χ2 = 3.15, p = 0.08, d = 0.27) but not for men (Log Rank: χ2 = 2.03, p = 0.16, d = 0.17). There were no significant effects of sex on the frequency of adverse events reported for the combined-dose or between-dose analysis (all p > 0.44). Conclusion: Baclofen significantly delayed the time to lapse for women but not male participants. These findings provide some support for the hypothesis that sex may be a potential moderator of baclofen response in the treatment of AUD. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01711125, identifier: NCT01711125.

Daily experiences of hangover severity and food consumption in young adults.

OBJECTIVES: Our aim was to determine whether alcohol hangover is associated with eating unhealthy foods (hot chips, soft drink) or healthy foods (fruit, vegetables). DESIGN: Daily diary study across 13 days (micro-longitudinal design). METHODS: We examined a sample of 605 young adults (71% women; ages 17-25; mean age 19.91 [SD 1.86] years) who completed daily diaries in the university community and reported drinking alcohol at least twice during the 13-day study period. Each day, participants reported on their hangover severity, their consumption of fruit, vegetables, hot chips (French fries), and soft drink, and their alcohol consumption from the previous day. Linear mixed models were used to examine within-person associations between hangover severity and food consumption, by gender. Exploratory models also controlled for previous day alcohol consumption to acknowledge potential variability in hangover susceptibility. RESULTS: On days when participants reported higher severity of hangovers, they reported consuming more hot chips (ß = .09, p = .001), more soft drink (ß = .08, p = .001) and less fruit (ß = -.06, p = .05). In our exploratory model controlling for previous day alcohol consumption, the predictive effect of hangover severity on hot chips remained (ß = .08, p = .009) and significant interaction effects were observed between gender and previous day alcohol consumption on fruit (ß = -.03, p = .003) and vegetable (ß = -.03, p = .03) servings. CONCLUSIONS: Higher hangover severity may lead to greater intake of some unhealthy foods such as hot chips, an effect that may not be reduceable to those associated with alcohol consumption per se. Interventions that target excessive drinking primarily, but also emphasize the importance of a healthy diet, should be considered for this population.

GABAB Receptors and Alcohol Use Disorders: Clinical Studies.

Harmful alcohol use and alcohol use disorders (AUD) result in major health and community burden worldwide, yet treatment options are limited. Novel pharmacotherapies are urgently required, and treatments involving GABAB receptors have been used in treating alcohol-related disorders. This chapter will review the clinical evidence of GABAB pharmacotherapies, such as baclofen and γ-hydroxybutyric acid. This includes the use of these treatments in individuals experiencing alcohol withdrawal symptoms and outlining the outcomes of studies of alcohol relapse prevention relapse including case studies, comparative studies and randomised controlled trials. Laboratory research investigating biobehavioural effects of baclofen will also be summarised and polymorphisms associated with baclofen treatment, and safety concerns of GABAB treatments will be addressed. In summary, pharmacological treatments targeting GABAB receptors such as baclofen may be modestly effective in the management of alcohol use disorder, but safety concerns limit the widespread applicability of the currently available agents.

Implementation of a Multi-Modal Training Program for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings: Pathways to Comorbidity Care (PCC).

OBJECTIVES: We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drugs (AOD) clinicians to improve the management of comorbidity. METHODS: A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined (a) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice (N = 10 clinical files per clinician), (b) self-efficacy, knowledge, and attitudes of clinicians. RESULTS: Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v -12% change from baseline, respectively; [X2 (1, N = 340) = 35.29, p = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [X2 (1, N = 340) = 10.45, p = .06]. There were significant improvements in the PCC relative to the control group for clinician self-efficacy, F(1,33) = 6.40, p = .02 and knowledge and attitudes of comorbidity monitoring, F(1,33) = 8.745, p = .01. CONCLUSIONS: The PCC training package may help improve identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity in drug and alcohol settings.

Online interventions for people hospitalized for deliberate self-harm and problematic alcohol use: Lessons learned from the iiAIM trial.

Deliberate self-harm and suicide affect all age groups, sexes, and regions, and their prevention is a global health priority. Acute alcohol misuse and chronic alcohol misuse are strong, modifiable risk factors, and Internet interventions aiming to reduce alcohol misuse and comorbid mental health problems (e.g., depression) are a promising and effective treatment modality. The research team aimed to evaluate the feasibility and effectiveness of an Internet-based comorbidity intervention primarily aiming to reduce alcohol consumption, and secondarily to reduce readmission for deliberate self-harm and improve psychological outcomes among people hospitalized for deliberate self-harm who also engage in problematic alcohol use. However, due to several barriers to recruitment, the trial could not be completed and was discontinued. The authors present a "Lessons Learned" discussion and describe the Internet Intervention for Alcohol Improvement (iiAIM) trial, discuss the key barriers experienced by the research team, and recommend potential solutions that may help future trials in this area.

High-dose baclofen attenuates insula activation during anticipatory anxiety in treatment-seeking alcohol dependant individuals: Preliminary findings from a pharmaco-fMRI study.

The GABA B agonist, baclofen, has been shown to reduce alcohol consumption in patients with alcohol use disorder and also those with comorbid anxiety. This study aimed to evaluate the effect of baclofen versus placebo on the BOLD response during an anticipatory anxiety fMRI task in treatment seeking alcohol patients. Participants included 28 alcohol dependant individuals who had received daily baclofen 30 mg (n = 10), 75 mg (n = 8) or placebo (n = 10) for at least 2 week on a randomized controlled trial (Morley, Leung et al. 2013, Morley, Baillie et al. 2018). Using functional magnetic resonance imaging (fMRI), we examined threat cue-elicited neural activation during a threat reactivity task 120 min following administration of BAC (30 mg or 75 mg) or placebo. Whole-brain analyses revealed no significant differences between the combined BAC doses versus PL. However, there were significant decreases in anticipatory threat cue-elicited activation observed in BAC 75 mg/day compared to PL participants in the insula. In response to threat cues, high dose (75 mg/day) baclofen administration attenuates activation in the insula and inferior frontal gyrus, relative to placebo. These preliminary findings suggests that modulating emotional regulation and attentional allocation during high threat stimuli may be mediated by GABA B receptors and may be a potential mechanism of action for baclofen's beneficial treatment effects for alcohol use disorder.