Search

Kirsten C Morley,1 Paul S Haber,1,2 Madeleine L Morgan,3 Fares Samara3,41Discipline of Addiction Medicine, Sydney Medical School, University of Sydney, NSW, Australia; 2Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 3Drug and Alcohol Services, North Coast Area Health Service, Kempsey and Port Macquarie, NSW, Australia; 4Durri Aboriginal Medical Service, Kempsey, NSW, AustraliaAbstract: Cannabis is one of the most widely used illicit drugs worldwide. However, while the rates of cannabis dependence and treatment increase, there remains no medications approved for this use. Due to its sedative effects and low abuse liability, the typical antipsychotic pericyazine has been utilized in some parts of Australia for the treatment of cannabis dependence. We aimed to provide documentation of preliminary outcomes and acceptability of pericyazine treatment in a small sample. A naturalistic case series study was conducted in which 21 patients were enrolled for a 4-week course of pericyazine (up to 8 × 2.5 mg tablets daily) and weekly medical review. Levels of cannabis use were reported and side effects with electrocardiography and blood tests were monitored. Measures of dependence severity, depression, anxiety, and insomnia were taken at baseline and follow-up utilizing validated psychometric tools. Significant reductions in cannabis use, depression, anxiety, and insomnia severity occurred across time. Pericyazine appeared to be well tolerated and easily administered in the community clinics. The results provide some preliminary evidence that low-dose short-term pericyazine may be an acceptable mode of treatment in this population. Given the open-label nature of the design, we cannot conclude that pharmacotherapy was uniquely responsible for the treatment effect. Nonetheless, low-dose pericyazine may be a potentially effective approach to the treatment of cannabis dependence, and further evaluation via a randomized placebo-controlled trial is warranted.Keywords: cannabis, antipsychotic, pharmacotherapy, addiction, pericyazine

Topiramate has been found to be effective in reducing alcohol use and may also attenuate anxiety severity in patients with alcohol use disorder (AUD). This study compared the neural response of treatment-seeking patients with AUD on either topiramate or naltrexone during an anticipatory anxiety task. Participants were 42 patients with AUD who were randomized to receive either topiramate (n = 23; titrated dose up to 200 mg/day) or naltrexone (n = 19; 50 mg/day) for 12-weeks as part of a larger randomized controlled trial. Following 6 weeks of treatment, participants completed an anticipatory anxiety task during a functional magnetic resonance imaging (fMRI) session. The task presented a series of high-threat and low-threat stimuli followed by an unpleasant or pleasant image, respectively. Primary whole-brain analyses revealed no significant differences in neural activation between the topiramate and naltrexone groups. Deactivation for safe cues relative to threat cues was observed within the precuneus, inferior parietal lobule and the cingulate gyrus. In the precentral and middle frontal gyri, threat cues elicited greater activation. Exploratory analyses revealed an effect of change in anxiety from baseline to week 6, with a greater reduction associated with a reduced response to threat cues relative to safe cues in the cuneus and lingual gyrus. The current study is the first to examine and compare neural activation during anticipatory anxiety in treatment-seeking individuals on topiramate and naltrexone. This preliminary research contributes to our understanding of the therapeutic mechanisms of these alcohol pharmacotherapies., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press.)

Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving. Methods : In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared. The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder. ClinicalTrials.gov Identifier: NCT05387148., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 Published by Elsevier Inc.)

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., (© 2024. The Author(s).)

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., Competing Interests: Dr. Kranzler has served on advisory boards for Dicerna Pharmaceuticals, Sophrosyne Pharmaceuticals, Entheon Pharmaceuticals, and Clearmind Medicine and as a consultant for Sobrera Pharmaceuticals; he has received research funding and medication supplies for an investigator-initiated study from Alkermes; he is a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, Otsuka, and Pear Therapeutics; and he is a holder of a patent for genotype-guided dosing of opioid agonists (U.S. 10,900,082). Dr. Tremonti has served as a speaker for Invidior. Dr. Haber has received research funding from Invidior. The other authors report no financial relationships with commercial interests.

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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 (M age  = 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., (© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

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., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 JBI. Unauthorized reproduction of this article is prohibited.)

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., (© 2023 Research Society on Alcohol.)

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.

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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

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., (© 2022. The Author(s).)

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 (β = .09, p = .001), more soft drink (β = .08, p = .001) and less fruit (β = -.06, p = .05). In our exploratory model controlling for previous day alcohol consumption, the predictive effect of hangover severity on hot chips remained (β = .08, p = .009) and significant interaction effects were observed between gender and previous day alcohol consumption on fruit (β = -.03, p = .003) and vegetable (β = -.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., (© 2021 British Psychological Society.)

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: χ 2 = 6.23, p = 0.01, d = 0.49) but not for men (Log Rank: χ 2 = 2.48, p = 0.12, d = 0.22) and a marginal effect of baclofen for days to first relapse for women (Log Rank: χ 2 = 3.15, p = 0.08, d = 0.27) but not for men (Log Rank: χ 2 = 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morley, Louie, Hurzeler, Baillie, Dore, Phung and Haber.)

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 GABA B receptors have been used in treating alcohol-related disorders. This chapter will review the clinical evidence of GABA B 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 GABA B treatments will be addressed. In summary, pharmacological treatments targeting GABA B 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., (© 2020. Springer Nature Switzerland AG.)

Background: We have previously reported that the Pathways to Comorbidity Care (PCC) training program for alcohol and other drug (AOD) clinicians improved identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity. We aimed to identify barriers and facilitators of implementation of the PCC training program in drug and alcohol settings. Methods: The PCC training program was implemented across 6 matched sites in Australia as per (1), and 20 clinicians received training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined barriers and facilitators of implementation according to the Consolidated Framework for Implementation Research. Results: Barriers included inner setting (e.g., allocated time for learning) and characteristics of individuals (e.g., resistance). Facilitators included intervention characteristics (e.g., credible sources), inner setting (e.g., leadership), and outer setting domains (e.g., patient needs). Clinical champions were identified as an important component of the implementation process. Conclusions: Barriers included limited specific allocated time for learning. A credible clinical supervisor, strong leadership engagement and an active clinical champion were found to be facilitators of the PCC training program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Louie, Giannopoulos, Baillie, Uribe, Wood, Teesson, Childs, Rogers, Haber and Morley.)

Of Recommendations and Levels of Evidence: Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity-frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient's needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the "teach-back" technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A)., Summary of Key Recommendations and Levels of Evidence: Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A)., (© 2021 AMPCo Pty Ltd.)

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; [ X 2 (1, N  = 340) = 35.29, p = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [ X 2 (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.

introduction : The number of medications approved for AUD is small and they generally have limited efficacy. We need new pharmacotherapies for the management of AUD. Areas covered : In this review, the authors aim to synthesise literature for new approved and emerging pharmacotherapies for AUD. Recently approved medications include nalmefene, which was approved in Europe and Australia for the purposes of controlled drinking. Baclofen has also been approved in France but not in other countries. Off label medications including topiramate and gabapentin have received significant attention with multiple RCTs and meta-analyses and have widespread use in several countries including the USA. Several novel medications have emerged over the last decade but further work is required to determine their efficacy and safety for the widespread management of AUD. Expert opinion : Despite significant advances in our understanding of the neurobiological basis of factors that contribute to the development and maintenance of AUD, there have been few new AUD medications approved for almost 20 years. There are many challenges to the development and introduction of new pharmacotherapies for AUD. Strategies for improving the translational pipeline include drug repurposing and utilisation of human acute laboratory models.

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., Competing Interests: Conflict of interest None., (Copyright © 2021. Published by Elsevier B.V.)

Rationale: Baclofen has been shown to effect fMRI alcohol cue reactivity in alcohol dependence, but potential varying effects related to baclofen dose levels have not been examined., Objective: This study investigated whether baclofen attenuates craving and alcohol cue-elicited activation in alcohol-dependent treatment seekers, and the relationship between this response and clinical outcomes (Morley et al. 2018; Morley et al. 2013)., Methods: Participants included 30 alcohol-dependent individuals who had received daily baclofen 30 mg (n = 11), 75 mg (n = 8) or placebo (n = 11) for at least 2 weeks. Using functional magnetic resonance imaging (fMRI), we examined alcohol cue-elicited neural activation during a visual alcohol cue reactivity task 120 min following treatment administration, and alcohol cue reactivity and percentage of heavy drinking days (% HDD) associations were assessed., Results: Both baclofen-treated groups reported fewer post-scan % HDD when compared to the placebo-treated group, but no subjective craving group differences were found. Increased alcohol cue-elicited activation was seen in placebo compared to the 75 mg/day baclofen participants in two clusters spanning prefrontal regions implicated in cue reactivity, chiefly frontal regions (i.e., frontal and precentral gyri, anterior cingulate cortex), but no observed alcohol cue reactivity differences between placebo and 30 mg/day baclofen groups. Post-scan % HDD was positively correlated with increased alcohol cue-elicited activation in a cluster encompassing the bilateral caudate nucleus and dorsal anterior cingulate cortex when comparing placebo versus 75 mg/day baclofen groups, and several clusters including prefrontal and mesolimbic regions when comparing placebo versus 30 mg/day baclofen groups., Conclusions: Baclofen administration attenuates alcohol cue-elicited activation and reduced the association in baclofen-treated participants between increased activity in key drug cue reactivity regions and higher post-scan % HDD observed in placebo-treated participants, suggesting a dose-specific response effect that may lead to reduced heavy drinking in chronic alcohol-dependent individuals., Trial Registration: ClinicalTrials.gov , NCT01711125, https://clinicaltrials.gov/ct2/show /NCT01711125.

Background: There is a paucity of translational research programmes to improve implementation of evidence-based care in drug and alcohol settings. This systematic review aimed to provide a synthesis and evaluation of the effectiveness of implementation programmes of treatment for patients with drug and alcohol problems using the Consolidated Framework for Implementation Research (CFIR)., Methods: A comprehensive systematic review was conducted using five online databases (from inception onwards). Eligible studies included clinical trials and observational studies evaluating strategies used to implement evidence-based psychosocial treatments for alcohol and substance use disorders. Extracted data were qualitatively synthesised for common themes according to the CFIR. Primary outcomes included the implementation, service system or clinical practice. Risk of bias of individual studies was appraised using appropriate tools. A protocol was registered with (PROSPERO) (CRD42019123812) and published previously (Louie et al. Systematic 9:2020)., Results: Of the 2965 references identified, twenty studies were included in this review. Implementation research has employed a wide range of strategies to train clinicians in a few key evidence-based approaches to treatment. Implementation strategies were informed by a range of theories, with only two studies using an implementation framework (Baer et al. J Substance Abuse Treatment 37:191-202, 2009) used Context-Tailored Training and Helseth et al. J Substance Abuse Treatment 95:26-34, 2018) used the CFIR). Thirty of the 36 subdomains of the CFIR were evaluated by included studies, but the majority were concerned with the Characteristics of Individuals domain (75%), with less than half measuring Intervention Characteristics (45%) and Inner Setting constructs (25%), and only one study measuring the Outer Setting and Process domains. The most common primary outcome was the effectiveness of implementation strategies on treatment fidelity. Although several studies found clinician characteristics influenced the implementation outcome (40%) and many obtained clinical outcomes (40%), only five studies measured service system outcomes and only four studies evaluated the implementation., Conclusions: While research has begun to accumulate in domains such as Characteristics of Individuals and Intervention Characteristics (e.g. education, beliefs and attitudes and organisational openness to new techniques), this review has identified significant gaps in the remaining CFIR domains including organisational factors, external forces and factors related to the process of the implementation itself. Findings of the review highlight important areas for future research and the utility of applying comprehensive implementation frameworks.

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.

Objective: We aimed to provide a synthesis and evaluation of psychosocial interventions to prevent suicide and reduce self-harm, as well as alcohol intake, for patients with alcohol problems., Methods: The systematic review was carried out according to the PRISMA guidelines and considered articles published in English from all countries. Terms relating to suicidality and alcohol problems were used to search Medline, EMBASE and PsycINFO databases. Randomized controlled trials of psychosocial interventions targeted for outpatient settings were included., Results: Six studies with a total of 400 participants were included. Two investigated dialectic behavioural therapy (DBT), one internet-delivered DBT, one dynamic deconstructivist psychotherapy (DDP) and two integrated cognitive behavioural therapy (CBT). Face to face and online DBT was significantly associated with abstinence and reductions in consumption with only a trend for a reduction in suicide attempts in one study relative to treatment at usual (TAU). DDP yielded significant reductions in alcohol consumption and suicide attempts versus community care. CBT was significantly effective relative to TAU in reducing alcohol use and suicide attempts in one trial with adolescents but not in another trial in an adult population., Conclusion: Integrated CBT has promise for adolescents, DBT may be helpful for alcohol patients with borderline personality disorder and iDBT may be useful for the wider community with heavy alcohol use. However, given the paucity of studies and the exploratory nature of these trials, there is currently no strong evidence for an effective psychosocial intervention to reduce alcohol consumption and suicidal behaviour in adults with problematic alcohol use., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Risk behaviors for young adults such as alcohol use are associated with increased risk of morbidity and mortality. Patterns of risk behavior may be genetically determined and vary between genders. Previous studies in both young adults and heavy drinking adult samples have demonstrated that some genotypes, such as OPRM1 A118G, COMT Val158Met and DRD2 Taq1A and DRD4 C52IT, may predict addictive behaviors including alcohol consumption and impulsivity, although results have been mixed. Methods: This study aimed to investigate the predictive relationship of these four single nucleotide polymorphisms (SNPs) prospectively on student patterns of drinking using a micro-longitudinal daily diary design in a sample of 628 young adults ages 18-25 of predominantly of European ethnicity. Linear mixed models were used to examine the effect of SNPs on the number of drinks per drinking session with gender as a moderating variable. Results: There were no main effects for genotype on alcohol consumption, nor for gender × genotype for any of the SNPs. There was a trend for an effect of the DRD2 Taq1A on the number of drinks per drinking day and for the interaction of gender and DRD2 Taq1A on the number of drinks per drinking day. Conclusion: These findings suggest that the DRD2 Taq1A , OPRM1 A118G, DRD4 C521T, or COMT Val158Met polymorphisms, are not associated with alcohol consumption in young adults, although there may be a relationship between DRD2 Taq1A and alcohol consumption in young adult males., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Chung, Logge, Riordan, Haber, Merriman, Phipps-Green, Topless, Merriman, Conner and Morley.)

Background: Pharmacological and behavioural treatments for alcohol use disorders (AUDs) are effective but the uptake is limited. Primary care could be a key setting for identification and continuous care for AUD due to accessibility, low cost and acceptability to patients. We aimed to synthesise the literature regarding differential models of care for the management of AUD in primary health care settings., Methods: We conducted a systematic review of articles published worldwide (1998-present) using the following databases; Medline, PsycINFO, Cochrane database of systematic reviews, Cochrane Central Register of Controlled Trials and Embase. The Grey Matters Tool guided the grey literature search. We selected randomised controlled trials evaluating the effectiveness of a primary care model in the management of AUD. Two researchers independently assessed and then reached agreement on the included studies. We used the Cochrane risk of bias tool 2.0 for the critical appraisal., Results: Eleven studies (4186 participants) were included. We categorised the studies into 'lower' versus 'higher' intensity given the varying intensity of clinical care evaluated across the studies. Significant differences in treatment uptake were reported by most studies. The uptake of AUD medication was reported in 5 out of 6 studies that offered AUD medication. Three studies reported a significantly higher uptake of AUD medication in the intervention group. A significant reduction in alcohol use was reported in two out of the five studies with lower intensity of care, and three out of six studies with higher intensity of care., Conclusion: Our results suggest that models of care in primary care settings can increase treatment uptake (e.g. psychosocial and/or pharmacotherapy) although results for alcohol-related outcomes were mixed. More research is required to determine which specific patient groups are suitable for AUD treatment in primary health care settings and to identify which models and components are most effective., Trial Registration: PROSPERO: CRD42019120293 .

Background: The dissemination and adoption of research into clinical practice in health care settings is a complex and challenging process. Clinical champions have been increasingly used in health care to facilitate the implementation and adoption of evidence-based practice and to overcome organizational barriers. In relation to substance use and mental health disorders, translation of new evidence into practice is an ongoing challenge. The utilization of a clinical champion to motivate staff to implement evidence-based practice in these settings may improve treatment quality and reduce the burden of disease. We thus aimed to conduct a systematic review to examine the role and efficacy of clinical champions in the drug and alcohol and mental health settings., Methods: We conducted a systematic literature search (1980-present) using the following databases: PubMed and PsycINFO. Additional studies were identified using reference searches of relevant reviews., Results: Thirteen separate studies were included in the final review. Clinical champions were typically selected rather than emergent, including clinical staff members engaging in a professional clinical role (e.g., physicians, psychologists, social workers). Training provided for these roles was often not stated. Clinical champions assisted with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation., Conclusions: In the substance use and mental health field, clinical champions appear to be an important component to facilitating practice changes. Future studies should provide specific details regarding attributes and training and also examine the relevant combination of personal characteristics and training sufficient to facilitate implementation of evidence-based practice in drug and alcohol and mental health settings., Plain Language Abstract: Treatment delivery in drug and alcohol and mental health settings may not always be based on best available evidence. Organizational context and individual factors are important in determining whether new practices will be adopted. Passive approaches such as websites or treatment manuals do not necessarily lead to change in practice. The clinical champion model has been shown to be effective in aiding implementation of evidence-based practice in health care settings. However, there is limited evidence evaluating its use in drug and alcohol and mental health settings. The current review aims to synthesize and evaluate the use of clinical champions in implementation research in drug and alcohol and mental health settings. We found that clinical champions were typically clinical staff members engaging in a professional clinical role. Training provided for these roles was often limited. Clinical champions may assist with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

There has been emerging interest in the role of the immune system in the pathophysiology of alcohol use disorder (AUD) given alcohol consumption stimulates immune cells to secrete peripheral pro- and anti-inflammatory cytokines. We conducted a systematic review and meta-analysis to determine whether an abnormal inflammatory cytokine profile exists in AUD patients compared to controls and whether cytokine levels were correlated with behavioural and psychiatric variables. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a comprehensive search of electronic databases (MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library) was conducted, for AUD-related terms in combination with cytokine-related terms. Patients had to meet established criteria for AUD and be compared with healthy controls. A critical appraisal was completed using the Newcastle-Ottawa Scale. Twenty-four papers met the inclusionary criteria with 46 serum or plasma cytokines measured without immune stimulation whereby 17 studies had sufficient data for inclusion in the meta-analysis. Collectively, AUD patients had greater cytokine concentrations than control patients g = 0.85 [ 95% CI 0.42, 1.29]. Differences in cytokine concentrations between AUD patients and controls varied within-study by stage of illness (R (2) 2  = 19.56%). The greatest differences were reported when AUD patients were engaging in active drinking g = 0.96 [0.49, 1.43] or were in alcohol withdrawal g = 1.25 [0.71, 1.80]. Baseline findings were moderated within and between studies by cytokine identity R (2) 2  = 51.10%; R (3) 2  = 44.89%. Cytokine concentrations were not significantly correlated with self-reported craving for alcohol, but were with alcohol consumption r = 0.22 [-0.05, 0.46]. The relationship between cytokine concentration and consumption was moderated by cytokine identity (R (2) 2  = 100.00%; R (3) 2  = 100.00%), and sample age (R (2) 2  = 0.00%; R (3) 2  = 95.76%). There is sufficient evidence to support the presence of an abnormal circulating cytokine profile in AUD which may vary with respect to the different stages of AUD illness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether baclofen-treated alcohol dependent participants show different subjective and psychophysiological responses to appetitive cues during an alcohol cue reactivity task compared to placebo, and whether these responses are associated with prospective drinking outcomes., Methods: Forty-two alcohol dependent participants (placebo: n = 12, low-dose baclofen [30 mg/day] n = 18, high-dose baclofen [75 mg/day]: n = 12) completed an alcohol cue reactivity task, whereby water and alcohol beverage cues were presented, with subsequent recovery periods, and subjective alcohol craving and psychophysiological indices (skin conductance; cardiovascular measures: heart rate, high-frequency heart rate variability) were recorded., Results: High-dose baclofen-treated participants showed both overall cue reactivity to water and alcohol cues and greater recovery effects during recovery periods, revealed by high-frequency heart rate variability, when compared to low-dose- and placebo-treated participants. There were no medication effects on subjective craving. In high-dose baclofen participants only, there was a predictive effect of lower baseline heart rate variability and fewer post-test percentage of heavy drinking days., Conclusion: There was a dose-specific rescuing effect of high-dose baclofen on the dynamic modulation of cardiovascular responses to eliciting cues. Investigation of treatment responses using psychophysiological techniques may elucidate baclofen's mechanisms of action, and identify subgroups amenable to treatment., (© 2020 John Wiley & Sons Ltd.)

Introduction : Chronic alcohol consumption has been observed to be associated with a range of cognitive impairments that impact on treatment management. In this spectroscopy study, we examined the association of N-Acetyl Aspartate (NAA), a marker of neuronal integrity, and cognitive impairment in alcohol dependent patients. Method : Using in vivo proton magnetic resonance spectroscopy ( 1 H-MRS), we examined brain metabolite levels in 31 alcohol dependent individuals. 1 H-MRS from the parietal lobe were analyzed to yield absolute concentrations of NAA. Alcohol history, neurocognitive function including Clock Drawing Test (CDT), Mini Mental State Exam (MMSE), Trial Making Test (TMT) and Balloon Analogue Risk Task (BART) were also assessed. Covariates included concurrent medication, age and recent alcohol consumption. Results : There were statistically significant bivariate associations between NAA and the variables age, CDT and BART (r = -.45, P = 01; r = -.53, P = .01; r = .49, P = .02) respectively) but there were no statistically significant associations with other measures of cognitive function. Controlling for age, concurrent medication and recent alcohol consumption, multiple linear regression revealed a negative association between parietal NAA (Model: F = 6.96, R 2  = .66, P = .001) and CDT scores ( B = -.35, P = .03), a positive association with BART scores ( B = .47, P = .02). Conclusion : These results demonstrate that in alcohol dependent patients lower NAA/Cr is associated with reduced cognitive functioning and increased risk-taking.

Background: Whilst effective treatments exist for substance use and alcohol use disorders, they are not commonly practised. Studies have shown that only a small percentage of services provide evidence-based treatments such as addiction medications or psychosocial therapies. Although there is a growing body of literature on evidence-based treatment, no synthesis of research on the implementation of evidence-based addiction treatment exists. This proposed systematic review will synthesise and evaluate the effectiveness of implementation programmes in the treatment of patients with drug and alcohol problems using the Consolidated Framework for Implementation Research (CFIR) framework., Methods: We will search (from inception onwards) PubMed/MEDLINE, Cochrane Library, PsycINFO, Web of Science and CINAHL. Eligible studies will be clinical trials (e.g. randomised controlled trials, non-randomised controlled trials) and observational studies (e.g. before-and-after studies, interrupted time series) evaluating strategies used to implement evidence-based psychosocial treatments for alcohol and substance use disorders. The primary outcomes will be related to the implementation, service system, or clinical practice (e.g. acceptability, implementation costs, feasibility). Two researchers will independently screen all citations, full-text articles and abstract data. Risk of bias of individual studies will be appraised using appropriate tools. A narrative synthesis will be provided., Discussion: This project aims to provide evidence to help guide the design of translational research programmes to improve implementation of evidence-based care in drug and alcohol settings. Findings from the study will specify effective strategies for domains of influence including (1) intervention characteristics (e.g. evidence strength and quality, adaptability), (2) outer setting (e.g. patient needs and resources, external policies and incentives), (3) inner setting (e.g. implementation climate, readiness for implementation), (4) individuals involved (e.g. self-efficacy, knowledge and beliefs about the intervention) and (5) the implementation process (e.g. engaging members of the organisation, executing the innovation). Identified gaps in knowledge will guide further study., Systematic Review Registration: PROSPERO CRD42019123812.

Background and Aims: Baclofen, a selective γ-aminobutyric acid (GABA) B receptor agonist, has emerged as a potential treatment for alcohol use disorder with much unexplained variation in response to treatment efficacy and dose regimen. Several positive studies include patients with alcoholic liver disease (ALD) and/or history of heavy drinking. The aim of this paper was to examine the association of cortical GABA+ concentration with severity of liver disease (including markers of liver injury) and other clinical characteristics in alcohol patients., Methods: Proton magnetic resonance spectroscopy ( 1 H-MRS), from the parietal lobe, was analyzed to yield absolute concentration of GABA in 24 alcohol-dependent individuals. Diagnosis of ALD, markers of liver injury, severity of liver disease (Model for End-Stage Liver Disease [MELD]), and alcohol history were assessed. Covariates included concurrent medication, age, and recent alcohol consumption., Results: Multiple linear regression revealed that GABA+ concentration was significantly predicted by MELD scores (F = 5.02, R 2  = 0.59, P = 0.01; MELD: B = -0.63, P = 0.02), when controlling for covariates concurrent medication, age, and recent alcohol consumption., Conclusion: Severity of ALD is associated with lower cortical concentrations of GABA+. These results may explain variations in response to the GABA B agonist, baclofen, in the alcohol-dependent population., (© 2018 Society for the Study of Addiction.)

Background: Alcohol use disorder (AUD) is highly prevalent and accounts globally for 1.6% of disability-adjusted life years (DALYs) among females and 6.0% of DALYs among males. Effective treatments for AUDs are available but are not commonly practiced in primary health care. Furthermore, referral to specialized care is often not successful and patients that do seek treatment are likely to have developed more severe dependence. A more cost-efficient health care model is to treat less severe AUD in a primary care setting before the onset of greater dependence severity. Few models of care for the management of AUD in primary health care have been developed and with limited implementation. This proposed systematic review will synthesize and evaluate differential models of care for the management of AUD in primary health care settings., Methods: We will conduct a systematic review to synthesize studies that evaluate the effectiveness of models of care in the treatment of AUD in primary health care. A comprehensive search approach will be conducted using the following databases; MEDLINE (1946 to present), PsycINFO (1806 to present), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) (1991 to present), and Embase (1947 to present). Reference searches of relevant reviews and articles will be conducted. Similarly, a gray literature search will be done with the help of Google and the gray matter tool which is a checklist of health-related sites organized by topic. Two researchers will independently review all titles and abstracts followed by full-text review for inclusion. The planned method of extracting data from articles and the critical appraisal will also be done in duplicate. For the critical appraisal, the Cochrane risk of bias tool 2.0 will be used., Discussion: This systematic review and meta-analysis aims to guide improvement of design and implementation of evidence-based models of care for the treatment of alcohol use disorder in primary health care settings. The evidence will define which models are most promising and will guide further research., Protocol Registration Number: PROSPERO CRD42019120293.

Alcohol-dependent individuals are often reported to use behavioral strategies both to escape from and avoid negative affective states, and also to approach positive affective states. However, there has been little examination of how these individuals acquire and express these types of behaviors. In this study, male adults meeting the International Classification of Diseases-10th Revision (ICD-10) criteria for alcohol dependence recruited from an outpatient treatment clinic and healthy male controls were given a computer-based task to assess learning and performance of escape, avoidance, and approach behaviors. In this task, participants control a spaceship and can either gain points by shooting an enemy spaceship or hide in safe areas to escape or avoid on-screen aversive events. We found that patients with alcohol dependence exhibited greater escape and approach behaviors, tended to show greater avoidance behavior, and achieved higher total score on the computer task than healthy controls. This is the first demonstration of such behavioral differences in this population, supporting the overactivation of both positive and negative reinforcement systems in alcohol dependence, and suggesting that such behavioral biases are not limited to alcohol-related cues. The contribution of this work to behavioral assessment and therapeutic approaches, as well as possible future directions, are discussed.

Aim: To examine clinical predictors of treatment response to baclofen in patients with alcohol use disorder (AUD)., Methods: Data from a randomised controlled trial (RCT) (N = 104), in which AUD patients received placebo or baclofen (30 mg/day or 75 mg/day) for 12 weeks, were analysed to determine predictive effects of the following four clinical characteristics: alcoholic liver disease (ALD), baseline alcohol consumption, craving and anxiety. Treatment outcomes included: (i) time to lapse and (ii) time to relapse., Results: For both outcome measures, baclofen, irrespective of dose, was more effective when alcohol consumption was higher at baseline. Relative to placebo, baclofen increased time to first lapse in patients with higher baseline alcohol consumption (HR = 0.459, 95% CI = 0.219-0.962, P < 0.05). Similarly, baclofen increased time to first relapse in patients with higher alcohol consumption at baseline (HR = 0.360, 95% CI = 0.168-0.772, P < 0.05). There were no predictive effects of other baseline characteristics on time to lapse nor time to relapse. Directly comparing high dose of baclofen (75 mg/day) with low dose of baclofen (30 mg/day) revealed no differences with regards to predictors of baclofen response., Conclusion: Baclofen, relative to placebo, was more effective when alcohol consumption was higher at baseline., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30-80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an "off-label" prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.

Aim: To examine subjective and psychophysiological responses to appetitive cues during an alcohol cue reactivity task, and its relation to alcoholic liver disease and assess whether executive functioning is associated with appropriate regulation of cue-elicited responses in individuals with severe alcohol use disorder (AUD)., Methods: Seventeen treatment-seeking alcoholic liver disease patients and a control group of treatment-seeking severe AUD participants completed neuropsychological executive functioning measures (Stroop task; Trail-making test) and the cue reactivity task, whereby control (water) and alcohol beverage cues were presented, followed by respective recovery periods. Subjective alcohol craving and heart rate variability were recorded across the task., Results: Overall cue reactivity and consequent recovery after cue offset during the cue reactivity task was observed, and alcoholic liver disease participants demonstrated a reduced overall recovery effect. Better Stroop performance related to greater overall and alcohol-specific cue reactivity within the control AUD group, and alcoholic liver disease participants showed dysfunctional activity regardless of executive functioning performance. No group differences in recovery effects according to executive functioning performance were seen., Conclusion: Among patients with AUD, having alcoholic liver disease seems to reduce overall regulation of responses to eliciting cues. Executive functioning moderated the magnitude of responses during cue exposures in our AUD sample overall; having alcoholic liver disease did not appear to affect regulation related to executive functioning during recovery.

Background: Insomnia and excessive daytime sleepiness (EDS) are reported to be common in methadone maintenance treatment (MMT) but much less is known about these symptoms in buprenorphine maintenance treatment (BMT) and in women compared with men. Methods: Cross sectional study of recipients of BMT ( n  = 113, 47 women), MMT ( n  = 184, 94 women), people using opioids nonmedically (nonopioid agonist treatment, non-OAT: n  = 87, 31 women) and a reference group with no opioid use (RG; n  = 105, 53 women) in Australia. Measures included Athens Insomnia Scale, Epworth Sleepiness Scale, the Hospital Anxiety and Depression Scale, and other substance use. Results: Insomnia (Athens Insomnia Scale, total ≥10) was highly prevalent among all people who use opioids (BMT 46.0-68.1%; MMT 55.4-69.6%; non-OAT 58.6-80.5%), did not differ significantly among these groups, and was significantly associated with anxiety and depression. EDS (Epworth score >10) was found in 14.2% of BMT, 22.8% of MMT, 35.6% of non-OAT groups, and 11.4% of the RG, and was significantly associated with depression overall. Fewer people had Epworth score >15 indicating more severe EDS (BMT 4.4%, MMT 6.0%; non-OAT 13.8%; RG 1.9%). Insomnia and EDS did not differ by sex or by opioid dose, nor were they significantly associated with other drug use, housing stress or social security status. Conclusions: Insomnia was common in people receiving OAT and using opioids non-medically, and associated with anxiety and depression. Clinicians should consider the possibility of daytime sleepiness in people receiving BMT and MMT, and in people using opioids nonmedically.

Aim: to describe trends in baclofen reports to Australia's largest Poisons Information Centre (PIC) and present a case series detailing severity of overdoses., Short Summary: PBS data demonstrates baclofen use is increasing in Australia, while calls to NSWPIC illustrate an increase in number of exposures associated with toxicity. Baclofen toxicity may require prolonged intensive care admission. To minimize harms associated, especially with off-label baclofen prescribing for AUD, prescribers should pay careful attention to psychiatric comorbidities, and closely monitor treatment and dispensing., Methods: this is a retrospective observational study of baclofen overdoses reported to New South Wales PIC (NSWPIC) from January 1 2004 to 31 December 2016. In addition, referrals to a metropolitan toxicology service relating to baclofen toxicity from 2014 to 2017 were analysed. The number of Pharmaceutical Benefit Scheme (PBS) claims for baclofen were also reviewed., Results: during the 13-year study period, 403 cases of baclofen toxicity were reported to NSWPIC. There was a 230% increase in annual exposures over this period, 71% of patients were symptomatic, with 77% requiring hospitalization. Coingestants were reported in 53%, with 57% being psychoactive medications (including alcohol). An increase in number of baclofen dispensing episodes was also noted. From the five cases of deliberate self-harm reported to the metropolitan toxicology service, three obtained baclofen for management of alcohol use disorder (AUD) and required prolonged treatment in the intensive care unit (ICU)., Conclusions: NSWPIC data shows an increase in number of calls regarding intentional baclofen exposures in parallel with increase the number of baclofen PBS claims. These closely parallel the increase in dispensing of baclofen since 2008. Case studies presented reinforce the severity of baclofen toxicity. Together, they demonstrate the potential risk of harm of baclofen prescribing, and the greater need for caution. Baclofen should be considered carefully in patients high risk of overdose or be used only in specialist services with close monitoring.