The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Understanding the challenges of identifying, supporting, and signposting patients with alcohol use disorder in secondary care hospitals, post COVID-19: a qualitative analysis from the North East and North Cumbria, England.

BACKGROUND: Alcohol-related mortality and morbidity increased during the COVID-19 pandemic in England, with people from lower-socioeconomic groups disproportionately affected. The North East and North Cumbria (NENC) region has high levels of deprivation and the highest rates of alcohol-related harm in England. Consequently, there is an urgent need for the implementation of evidence-based preventative approaches such as identifying people at risk of alcohol harm and providing them with appropriate support. Non-alcohol specialist secondary care clinicians could play a key role in delivering these interventions, but current implementation remains limited. In this study we aimed to explore current practices and challenges around identifying, supporting, and signposting patients with Alcohol Use Disorder (AUD) in secondary care hospitals in the NENC through the accounts of staff in the post COVID-19 context. METHODS: Semi-structured qualitative interviews were conducted with 30 non-alcohol specialist staff (10 doctors, 20 nurses) in eight secondary care hospitals across the NENC between June and October 2021. Data were analysed inductively and deductively to identify key codes and themes, with Normalisation Process Theory (NPT) then used to structure the findings. RESULTS: Findings were grouped using the NPT domains 'implementation contexts' and 'implementation mechanisms'. The following implementation contexts were identified as key factors limiting the implementation of alcohol prevention work: poverty which has been exacerbated by COVID-19 and the prioritisation of acute presentations (negotiating capacity); structural stigma (strategic intentions); and relational stigma (reframing organisational logics). Implementation mechanisms identified as barriers were: workforce knowledge and skills (cognitive participation); the perception that other departments and roles were better placed to deliver this preventative work than their own (collective action); and the perceived futility and negative feedback cycle (reflexive monitoring). CONCLUSIONS: COVID-19, has generated additional challenges to identifying, supporting, and signposting patients with AUD in secondary care hospitals in the NENC. Our interpretation suggests that implementation contexts, in particular structural stigma and growing economic disparity, are the greatest barriers to implementation of evidence-based care in this area. Thus, while some implementation mechanisms can be addressed at a local policy and practice level via improved training and support, system-wide action is needed to enable sustained delivery of preventative alcohol work in these settings.

Driving under the influence of alcohol and alcohol use disorder: the relevance of early identification from an Italian retrospective outpatient study.

INTRODUCTION: Worldwide, almost 1.2 million people drive under the influence of alcohol. However, early identification of alcohol use disorder (AUD) in subjects driving under the influence (DUI) of alcohol is seldom achieved. AIM: The aim of our retrospective study is to investigate the presence of AUD in a population of DUI subjects who had their driving license suspended, and if they were following a specific rehabilitation program. METHODS AND RESULTS: 750 subjects were retrospectively enrolled from 2018 to 2021. DSM-V to assess AUD was used. Forty-eight (6.4%) subjects presented a diagnosis of AUD, after one month they showed a statistically significant reduction of carbohydrate-deficient transferrin (CDT) (p<0.0001); however, none were following a program for the treatment of AUD. CONCLUSIONS: This outpatient setting may be considered a place of primary and secondary prevention where DUI subjects with a diagnosis of AUD may be entrusted to a Centre in order to follow rehabilitation treatment.

Harm Reduction in Psychiatric Settings.

Public health announcements, the White House, and other government and private agencies have made progress in reducing the stigma associated with substance use disorders, and more Americans are seeking treatment. Yet only a small percentage of persons seeking treatment are receiving care. Many resources are now available to help nurse practitioners use a harm reduction approach to helping people understand their options and make choices. Harm reduction includes offering U.S. Food and Drug Administration-approved medications for treatment of tobacco use disorder, alcohol use disorder, and opioid use disorder. Drug mechanisms for acute and maintenance treatment are discussed. [Journal of Psychosocial Nursing and Mental Health Services, 62(7), 7-10.].

Agile implementation of alcohol screening in primary care.

BACKGROUND: Despite the United States Preventive Services Task Force recommendation to screen adults for unhealthy alcohol use, the implementation of alcohol screening in primary care remains suboptimal. METHODS: A pre and post-implementation study design that used Agile implementation process to increase screening for unhealthy alcohol use in adult patients from October 2021 to June 2022 at a large primary care clinic serving minority and underprivileged adults in Indianapolis. RESULTS: In comparison to a baseline screening rate of 0%, the agile implementation process increased and sustained screening rates above 80% for alcohol use using the Alcohol Use Disorders Identification Test - Consumption tool (AUDIT-C). CONCLUSIONS: Using the agile implementation process, we were able to successfully implement evidence-based recommendations to screen for unhealthy alcohol use in primary care.

Involvement of the gut microbiome-brain axis in alcohol use disorder.

The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome-brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.

AUDIT C compared to PEth in middle-aged volunteers.

AIMS: To compare Alcohol Use Disorders Identification Test (AUDIT C) to phosphatidylethanol (PEth) in middle-aged randomly selected volunteers. Apply previously suggested lower cut-offs for PEth using moderate alcohol intake according to AUDIT C as a reference. METHODS: Within the Swedish CardioPulmonary BioImage Study, 2255 middle-aged (50-64 years of age) volunteers in northern Sweden participated in comparing AUDIT C to PEth 16:0/18:1. RESULTS: There was a moderate correlation between PEth 16:0/18:1 and AUDIT C (r = 0.66). None of the participants with the AUDIT C-score 0 had a measurable PEth. Of moderate alcohol consumers, according to AUDIT C (AUDIT C 1-3 women, 1-4 men), 96% had a PEth below 0.3 µmol/L, 91% had a PEth below 0.16 µmol/L, and 84% had a PEth below 0.11 µmol/L. With PEth equivalent to excessive alcohol consumption (≥0.3 µmol/L), 26% had an AUDIT C-score below excessive alcohol consumption (<4 for women and <5 for men). Thirty percent of patients with a PEth ≥0.16 µmol/L had an AUDIT C-score below excessive alcohol consumption, and 37% had a PEth ≥0.11 µmol/L. We found no significant correlation between BMI and PEth or AUDIT C. CONCLUSIONS: There is a significant correlation between AUDIT C and PEth. Using AUDIT C alone, 26% of high-consumers, according to PEth, are not found in our cohort, but an AUDIT C-score of 0 will exclude high consumption, according to PEth. Our findings support the current cut-off for PEth of 0.3 µmol/L, but a lower cut-off seems reasonable.

Equivalence of Alcohol Use Disorder Symptom Assessments in Routine Clinical Care When Completed Remotely via Online Patient Portals Versus In Clinic via Paper Questionnaires: Psychometric Evaluation.

BACKGROUND: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommends the paper-based or computerized Alcohol Symptom Checklist to assess alcohol use disorder (AUD) symptoms in routine care when patients report high-risk drinking. However, it is unknown whether Alcohol Symptom Checklist response characteristics differ when it is administered online (eg, remotely via an online electronic health record [EHR] patient portal before an appointment) versus in clinic (eg, on paper after appointment check-in). OBJECTIVE: This study evaluated the psychometric performance of the Alcohol Symptom Checklist when completed online versus in clinic during routine clinical care. METHODS: This cross-sectional, psychometric study obtained EHR data from the Alcohol Symptom Checklist completed by adult patients from an integrated health system in Washington state. The sample included patients who had a primary care visit in 2021 at 1 of 32 primary care practices, were due for annual behavioral health screening, and reported high-risk drinking on the behavioral health screen (Alcohol Use Disorder Identification Test-Consumption score ≥7). After screening, patients with high-risk drinking were typically asked to complete the Alcohol Symptom Checklist-an 11-item questionnaire on which patients self-report whether they had experienced each of the 11 AUD criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) over a past-year timeframe. Patients could complete the Alcohol Symptom Checklist online (eg, on a computer, smartphone, or tablet from any location) or in clinic (eg, on paper as part of the rooming process at clinical appointments). We examined sample and measurement characteristics and conducted differential item functioning analyses using item response theory to examine measurement consistency across these 2 assessment modalities. RESULTS: Among 3243 patients meeting eligibility criteria for this secondary analysis (2313/3243, 71% male; 2271/3243, 70% White; and 2014/3243, 62% non-Hispanic), 1640 (51%) completed the Alcohol Symptom Checklist online while 1603 (49%) completed it in clinic. Approximately 46% (752/1640) and 48% (764/1603) reported ≥2 AUD criteria (the threshold for AUD diagnosis) online and in clinic (P=.37), respectively. A small degree of differential item functioning was observed for 4 of 11 items. This differential item functioning produced only minimal impact on total scores used clinically to assess AUD severity, affecting total criteria count by a maximum of 0.13 criteria (on a scale ranging from 0 to 11). CONCLUSIONS: Completing the Alcohol Symptom Checklist online, typically prior to patient check-in, performed similarly to an in-clinic modality typically administered on paper by a medical assistant at the time of the appointment. Findings have implications for using online AUD symptom assessments to streamline workflows, reduce staff burden, reduce stigma, and potentially assess patients who do not receive in-person care. Whether modality of DSM-5 assessment of AUD differentially impacts treatment is unknown.

Associations between mental health & substance use treatment and alcohol use progression and recovery among US women drinkers.

BACKGROUND: Alcohol use has profound public health impact on women; however, modifiable factors that may influence alcohol use progression/recovery, including health service utilization, are understudied in women. OBJECTIVE: To investigate the association between mental health (MH) and substance use (SU) treatment with alcohol use progression and recovery among women who currently use alcohol or have in the past. METHODS: This study is a secondary data analysis of prospective data from waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; a US-nationally representative sample of adults). The analytic sample was limited to women who reported past or current alcohol use at wave 1 (N = 15,515). Latent transition analysis (LTA) examined whether receiving SU/MH treatment in the year prior to wave 1 was associated with transitioning between three empirically-derived stages of alcohol involvement (no, moderate, and severe problems classes), between Waves 1 and 2 adjusting for possible confounders using propensity score weight. RESULTS: Compared to White female drinkers, female drinkers who were from Black, Hispanic, or other races were less likely to receive SU/MH treatment (p-values ≤. 001). SU/MH treatment in the year prior to wave 1 was associated with transitioning from the moderate problems class to the no problems class between Waves 1 and 2 (p-value = .04). CONCLUSION: Receipt of SU or MH treatment among women, was associated with a higher likelihood of remission from moderate alcohol use problems to no problems over time. Future research, including investigation into treatment characteristics (e.g., frequency, duration, type) should further explore why women initially experiencing severe alcohol use problems did not experience similar remission.

Hospitalizations for mental and behavioral disorders due to alcohol and other psychoactive substance use among adolescents in Brazil, 2017-2022.

OBJECTIVE: To assess the epidemiological profile and trend in hospitalizations for mental and behavioral disorders due to alcohol and other psychoactive substance use among Brazilian adolescents, between 2017 and 2022. METHODS: This was a time-series study using data from the Hospital Information System of the Brazilian National Health System; the trend analysis was performed by estimating the annual percentage change (APC) of hospitalization rates per 100,000 inhabitants and respective confidence intervals (95%CI), using the Prais-Winsten method. RESULTS: A total of 29,991 hospitalizations were recorded in the study period, with a decreasing trend observed, from 16.18/100,000 inhabitants in 2017 to 13.72/100,000 inhab. in 2022 (percent change of -2.65%; 95%CI -4.47;-0.80), a greater decline was found in males (-3.48%; 95%CI -5.20;-1.72), in the age group of 15 to 19 years (-2.79%; 95%CI -4.49;-1.06), in the South (-3.29%; 95%CI -5.37;-1.16) and Midwest (-3.64%; 95%CI -5.75;-1.49) regions of the country. CONCLUSION: Hospitalizations showed a decreasing trend in the study period, with sociodemographic disparities.

No improvement in AUDIT-C screening and brief intervention rates among wait-list controls following support of Aboriginal Community Controlled Health Services: evidence from a cluster randomised trial.

BACKGROUND: While Aboriginal and Torres Strait Islander Australians are less likely to drink any alcohol than other Australians, those who drink are more likely to experience adverse alcohol-related health consequences. In a previous study, providing Aboriginal Community Controlled Health Services (ACCHSs) with training and support increased the odds of clients receiving AUDIT-C alcohol screening. A follow-up study found that these results were maintained for at least two years, but there was large variability in the effectiveness of the intervention between services. In this study, we use services that previously received support as a comparison group to test whether training and support can improve alcohol screening and brief intervention rates among wait-list control ACCHSs. METHODS: Design: Cluster randomised trial using routinely collected health data. SETTING: Australia. CASES: Twenty-two ACCHSs that see at least 1000 clients a year and use Communicare as their practice management software. Intervention and comparator: After initiating support, we compare changes in screening and brief intervention between wait-list control services and services that had previously received support. MEASUREMENT: Records of AUDIT-C screening and brief intervention activity in routinely collected data. RESULTS: During the reference period we observed 357,257 instances where one of 74,568 clients attended services at least once during a two-monthly data extraction period. Following the start of support, the odds of screening (OR = 0.94 [95% CI 0.67, 1.32], p = 0.74, [Formula: see text]≈ 0.002) and brief intervention (OR = 1.43 [95% CI 0.69, 2.95], p = 0.34, [Formula: see text]≈ 0.002) did not improve for the wait-list control group, relative to comparison services. CONCLUSIONS: We did not replicate the finding that support and training improves AUDIT-C screening rates with wait-list control data. The benefits of support are likely context dependent. Coincidental policy changes may have sensitised services to the effects of support in the earlier phase of the study. Then the COVID-19 pandemic may have made services less open to change in this latest phase. Future efforts could include practice software prompts to alcohol screening and brief intervention, which are less reliant on individual staff time or resources. TRIAL REGISTRATION: Retrospectively registered on 2018-11-21: ACTRN12618001892202.

Therapeutic Potential of Naltrexone in the Niche of Psychopharmacology.

NTX is FDA-approved for opiate and alcohol use disorders as anti-craving agent. It has been used successfully off-label in other psychiatric indications. Here, we shed some light on these while examining the extant evidence.

Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models.

Alcohol tolerance is a neuroadaptive response that leads to a reduction in the effects of alcohol caused by previous exposure. Tolerance plays a critical role in the development of alcohol use disorder (AUD) because it leads to the escalation of drinking and dependence. Understanding the molecular mechanisms underlying alcohol tolerance is therefore important for the development of effective therapeutics and for understanding addiction in general. This review explores the molecular basis of alcohol tolerance in invertebrate models, Drosophila and C. elegans, focusing on synaptic transmission. Both organisms exhibit biphasic responses to ethanol and develop tolerance similar to that of mammals. Furthermore, the availability of several genetic tools makes them a great candidate to study the molecular basis of ethanol response. Studies in invertebrate models show that tolerance involves conserved changes in the neurotransmitter systems, ion channels, and synaptic proteins. These neuroadaptive changes lead to a change in neuronal excitability, most likely to compensate for the enhanced inhibition by ethanol.

Bad habits-good goals? Meta-analysis and translation of the habit construct to alcoholism.

Excessive alcohol consumption remains a global public health crisis, with millions suffering from alcohol use disorder (AUD, or simply "alcoholism"), leading to significantly reduced life expectancy. This review examines the interplay between habitual and goal-directed behaviors and the associated neurobiological changes induced by chronic alcohol exposure. Contrary to a strict habit-goal dichotomy, our meta-analysis of the published animal experiments combined with a review of human studies reveals a nuanced transition between these behavioral control systems, emphasizing the need for refined terminology to capture the probabilistic nature of decision biases in individuals with a history of chronic alcohol exposure. Furthermore, we distinguish habitual responding from compulsivity, viewing them as separate entities with diverse roles throughout the stages of the addiction cycle. By addressing species-specific differences and translational challenges in habit research, we provide insights to enhance future investigations and inform strategies for combatting AUD.

Trend in mortality from mental and behavioral disorders due to alcohol use in Brazil, 2010-2021.

OBJECTIVE: To analyze the trend in mortality from mental and behavioral disorders due to alcohol use in Brazil, 2010-2021. METHODS: This was an time series study using Mortality Information System data. Annual percentage change (APC) and 95% confidence intervals (95% CI) were calculated using Prais-Winsten linear regression. RESULTS: Mortality showed a stationary trend for Brazil as a whole (APC = 0.6; 95%CI -4.2;3.0), a falling trend in individuals aged 20-29 years in the South (APC = -7.4; 95%CI -10.0;-4.3) and Northeast (APC = -3.4; 95%CI -6.4;-0.4) regions, in people aged 30-39 in the Midwest region (APC = -3,8; 95%CI -7.4;-0.1) and 40-49 in the South (APC = -2.1; 95%CI -3.8;-0.4), North (APC = -3.1; 95%CI -5.7;-0.5) and Midwest (APC = -2.9; 95%CI -5.5;-0.3) regions. CONCLUSION: Mortality from mental and behavioral disorders due to alcohol use showed a stationary trend nationally and a falling trend in some age groups regionally.

Neural responses to reward, threat, and emotion regulation and transition to hazardous alcohol use.

AIMS: Reward processing and regulation of emotions are thought to impact the development of addictive behaviors. In this study, we aimed to determine whether neural responses during reward anticipation, threat appraisal, emotion reactivity, and cognitive reappraisal predicted the transition from low-level to hazardous alcohol use over a 12-month period. METHODS: Seventy-eight individuals aged 18-22 with low-level alcohol use [i.e. Alcohol Use Disorder Identification Test (AUDIT) score <7] at baseline were enrolled. They completed reward-based and emotion regulation tasks during magnetic resonance imaging to examine reward anticipation, emotional reactivity, cognitive reappraisal, and threat anticipation (in the nucleus accumbens, amygdala, superior frontal gyrus, and insula, respectively). Participants completed self-report measures at 3-, 6-, 9-, and 12-month follow-up time points to determine if they transitioned to hazardous use (as defined by AUDIT scores ≥8). RESULTS: Of the 57 participants who completed follow-up, 14 (24.6%) transitioned to hazardous alcohol use. Higher baseline AUDIT scores were associated with greater odds of transitioning to hazardous use (odds ratio = 1.73, 95% confidence interval 1.13-2.66, P = .005). Brain activation to reward, threat, and emotion regulation was not associated with alcohol use. Of the neural variables, the amygdala response to negative imagery was numerically larger in young adults who transitioned to hazardous use (g = 0.31), but this effect was not significant. CONCLUSIONS: Baseline drinking levels were significantly associated with the transition to hazardous alcohol use. Studies with larger samples and longer follow-up should test whether the amygdala response to negative emotional imagery can be used to indicate a future transition to hazardous alcohol use.

Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.