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

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

Associations between smoking and pain in early recovery in residential substance use treatment-seekers.

INTRODUCTION: A growing literature indicates bidirectional associations between pain and tobacco use. Cigarette smokers are at increased risk for chronic pain, and observational and experimental studies indicate that pain increases motivation to smoke. Tobacco use disorder frequently co-occurs with other substance use disorders, which are also associated with chronic pain vulnerability. Despite evidence that pain significantly predicts smoking and relapse, associations between smoking history/trajectory and changes in pain over the course of treatment have not been characterized. The objective of the study was to determine the association between in-treatment smoking trajectory, pack-years (i.e., number of cigarette packs smoked per day multiplied by smoking duration), pain-related interference in daily activities, and pain intensity over the course of residential treatment. METHODS: In this study, 280 adult smokers in a residential SUD treatment center in North Central Florida completed questionnaires assessing cigarette use, pain intensity, and pain interference at treatment entry and discharge (Mean = 80.3 days, SD = 25.6). Most participants were diagnosed with alcohol use disorder (66.1 %). Opioid (27.9 %) and cannabis use disorders (29.6 %) were also common. Participants were grouped by whether their smoking increased (n = 36), decreased (n = 46), or stayed the same (n = 133) from entry to discharge. RESULTS: Analyses indicated a positive association between pack-years and pain intensity at both baseline (r = 0.185, p = 0.018) and discharge (r = 0.184, p = 0.019). Smoking trajectory was associated with pack-years, with those decreasing smoking having greater pack-years than those sustaining or increasing use [F(2,136) = 8.62, p < 0.01, η2p = 0.114]. Mixed general linear models indicated pain intensity [F(1,274) = 44.15, p < 0.0001, η2p = 0.138] and interference in day-to-day activities [F(1,276) = 31.79, p < 0.0001, η2p = 0.103] decreased significantly over time. However, there was no main effect of smoking trajectory on pain intensity [F(2,212) = 2.051, p = 0.131, η2p = 0.019] or of smoking trajectory by time interaction [F(2, 212) = 1.228, p = 0.295, η2p = 0.011]. CONCLUSIONS: Overall, findings provide evidence that smoking behavior influences pain within the context of residential substance use treatment. Given that pain is associated with urge to use substances and risk of return to use, more consistent and rigorous assessment of pain and proactive pain management is likely to enhance substance use treatment outcomes among people who smoke.

[Intended utilization of health care services in cases of mental illnesses with varying urgency]. / Intendierte Inanspruchnahme von Versorgungsangeboten bei psychischen Erkrankungen mit unterschiedlicher Dringlichkeit.

OBJECTIVE: To investigate variations in intended utilization in cases of an acute psychotic episode, an alcohol related or depressive disorder depending on different case characteristics. METHODS: A telephone survey with case vignettes was conducted (N=1,200). Vignettes varied in terms of urgency of symptoms, daytime, sex of the afflicted person and age/mental disorder. The respondents were asked to indicate whom they would contact first in the described case. RESULTS: Outpatient physicians were named most frequently as the first point of contact (61.1%) while only 6.5% of the respondents named emergency medicine including the medical on call service (8.1% in high urgency cases, i. e. emergencies that did not tolerate any delay). Intended utilization varied by urgency and age/mental illness. CONCLUSION: More Information about the need to seek medical help immediately in cases of mental illnesses with high urgency should be provided.

Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: a 12 week, randomized, double-blind, pilot study.

Topiramate (TPM), a GABA/glutamate modulator, has shown positive results for treating alcohol use disorder (AUD), but causes significant cognitive adverse effects. TPM causes cognitive side effects by reducing glutathione levels in the frontal lobe. N-acetyl cysteine (NAC) increases level of intracellular glutathione. We hypothesized that combining NAC with TPM may mitigate the possible cognitive side effects of TPM, as well as working synergistically in reducing alcohol consumption more efficaciously than using TPM alone. A 12-week, double-blind randomized trial assessing the effects of combining NAC (1200 mg/day) with TPM (200 mg/day) vs TPM alone (i) cognitive side effects caused by TPM, (ii) percentage of heavy drinking days (PHDD) and percentage of days abstinent (PDA) using weekly calendar, and (iii) craving outcomes using the obsessive-compulsive drinking scale. Seventeen participants were randomized into the study (nine received TPM + NAC and eight matching TPM + Placebo). Cognitive adverse events were not significantly different between the treatment arms (P = 0.581). There was no difference in PHDD (P = 0.536) and in PDA over the entire study period (P = 0.892). However, both treatment groups at study end, compared with the baseline, significantly reduced their PHDD and increased their PDA. As for cravings: TPM + NAC group has shown higher level in automaticity of drinking (P = 0.029) and interference due to drinking (P = 0.014) subscales compared with the TPM + Placebo group. No difference was observed between groups in terms of Drinking Obsessions and Alcohol Consumption subscales. This pilot study indicates that combining NAC with TPM is overall safe, but the addition of NAC has no significant benefit over placebo in the incidence of TPM-related cognitive impairment, and alcohol drinking. Furthermore, craving outcomes may become worse with the addition of NAC.

Psychiatric and substance use disorders among adults over age 50 who use cannabis: A matched cohort study using electronic health record data.

INTRODUCTION: Adults over age 50 increasingly use cannabis, but few studies have examined co-occurring psychiatric and substance use disorders (SUDs) in this population. The current study utilized electronic health record (EHR) data to compare adults age 50 + with ICD-10 cannabis codes (cases) and matched controls on common psychiatric and SUDs from 2016 to 2020. METHOD: Patients age 50 + from an integrated healthcare system in Hawai'i were identified using ICD-10 codes for cannabis (use, abuse, and dependence) from 2016 to 2018. In a matched cohort design, we selected non-cannabis-using controls (matched on sex and age) from the EHR (n = 275) and compared them to cases (patients with an ICD-10 cannabis code; n = 275) on depressive and anxiety disorders and SUDs (i.e., tobacco, opioid, and alcohol use disorders) over a two-year follow-up period. RESULTS: Participants were 62.8 years (SD = 7.3) old on average; and were White (47.8 %), Asian American (24.4 %), Native Hawaiian or Pacific Islander (19.3 %), or Unknown (8.5 %) race/ethnicity. Conditional multiple logistic regression was used to estimate odds ratios comparing cases vs controls. Participants with an ICD-10 cannabis code had a significantly greater risk of major depressive disorder (OR = 10.68, p < 0.0001) and any anxiety disorder (OR = 6.45, p < 0.0001), as well as specific anxiety or trauma-related disorders (e.g., generalized anxiety disorder, PTSD) and SUDs (ORs 2.72 - 16.00, p < 0.01 for all). CONCLUSIONS: Over a two-year period, diverse adults age 50 + in Hawai'i with ICD-10 cannabis codes experienced higher rates of subsequent psychiatric and SUDs compared to controls. These findings can guide efforts to inform older adults about possible cannabis-related risks.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Depressive symptoms and alcohol and marijuana use among adolescents / Sintomas depressivos e uso de álcool e maconha em adolescentes / Síntomas depresivos y uso de alcohol y marihuana en adolescentes

Risk behaviors are common in adolescence and demonstrates an association with depressive symptoms. Considering the psychological health implications of this phase in adult life, the aim of this study was to verify associations between depressive symptoms and consumption of alcohol and marijuana, self-injurious behavior, health self-perception, life satisfaction, anxiety symptoms and suicidal ideation in adolescents. A total of 298 adolescents, aged 12 to 14 years (61.1% girls), participated in the study. The measures were the translated Health Behavior in School-aged Children questionnaire (HBSC - BR) and the Children's Depression Inventory (CDI). The chi-square test, student's t test and binomial logistic regression (p<0.05) were used. Depressive symptoms were associated with anxiety symptoms and self-injury. Higher risk for alcohol use and consumption, self-injury, negative health self-perception, anxiety and depression related to females. The findings of this population suggest worrying health outcomes, especially for girl. (AU)

Comportamentos de risco são comuns na adolescência e demonstram associação com sintomas depressivos. Considerando as implicações da saúde psicológica dessa fase na vida adulta, o objetivo deste trabalho foi verificar associações entre sintomas depressivos e consumo de álcool e maconha, comportamento autolesivo, autopercepção de saúde, satisfação com a vida, sintomas ansiosos e ideação suicida em adolescentes. Participaram 298 adolescentes, de 12 a 14 anos (61,1% meninas). Os instrumentos utilizados foram o questionário traduzido Health Behavior in School-aged Children (HBSC - BR) e o Inventário de Depressão Infantil (CDI). Utilizou-se os teste Qui-Quadrado, t de student e regressão logística binomial (p<0,05). Sintomas depressivos associaram-se com sintomas ansiosos e autolesão. Maior risco para uso e consumo de álcool, autolesão, autopercepção de saúde negativa, ansiedade e depressão em relação ao sexo feminino. Os achados desta população sugerem resultados preocupantes de saúde, sobretudo para o sexo feminino. (AU)

Las conductas de riesgo son comunes en la adolescencia y demuestran una asociación con síntomas depresivos. Considerando las implicaciones psicológicas para la salud de esta fase en la vida adulta, el objetivo de este estudio fue verificar asociaciones entre síntomas depresivos y consumo de alcohol y marihuana, autolesión, autopercepción de salud, satisfacción con la vida, ansiedad e ideación suicida en adolescentes. Participaron 298 adolescentes de 12 a 14 años (61,1% niñas). Los instrumentos utilizados fueron el cuestionario traducido Health Behavior in School-aged Children (HBSC - BR) y el Inventario de Depresión Infantil (CDI). Se utilizaron las pruebas de chi-cuadrado, t de Student y regresión logística binomial (p<0,05). Los síntomas depresivos se asociaron con síntomas de ansiedad y autolesiones. Mayor riesgo de uso y consumo de alcohol, autolesiones, autopercepción negativa de la salud, ansiedad y depresión en relación con el sexo femenino. Los hallazgos de esta población sugieren resultados de salud preocupantes, especialmente para las mujeres. (AU)

Substance Use in U.S. Vietnam War Era Veterans and Nonveterans: Results from the Vietnam Era Health Retrospective Observational Study.

Background: Substance use (SU) is associated with physical injury and mental health disorders in older persons, but recent research has scarcely examined SU in U.S. Vietnam-era veterans who are mostly in or near their eighth decade of life. Objectives: We compared the prevalence of self-reported lifetime and current SU and modeled current usage patterns in a nationally representative sample of veterans versus a matched nonveteran cohort. Methods: Cross-sectional, self-reported survey data were analyzed from the 2016-2017 Vietnam Era Health Retrospective Observational Study (VE-HEROeS) (n = 18,866 veterans, n = 4,530 nonveterans). We assessed lifetime and current alcohol and drug use disorders; lifetime and current use of cannabis, opioids, stimulants, sedatives, "other drugs" (psychedelics, prescription or over-the-counter drugs not prescribed/used as intended); and current SU patterns (alcohol-use-only, drug-use-only, dual-SU, no SU). Weighted descriptive, bivariable, and multivariable statistics were calculated. Covariates in multinomial modeling included sociodemographic characteristics, lifetime cigarette smoking, depression, potentially traumatic events (PTEs), and current pain (SF-8TM). Results: Prevalence of lifetime opioid and sedative use (p ≤ .01), drug and alcohol use disorders (p < .001), and current "other drug" use (p < .001) were higher in veterans versus nonveterans. Current use of alcohol and cannabis was high in both cohorts. In veterans, very severe/severe pain, depression, and PTEs were highly associated with drug-use-only (p < .001) and dual-SU (p < .01), but these associations were fewer for nonveterans. Conclusion: This research confirmed existing concerns over substance misuse in older individuals. Vietnam-era veterans may be at particular risk due to service-related experiences and later-life tribulations. Era veterans' unique perceptions toward healthcare assistance for SU may need greater provider focus to maximize self-efficacy and treatment.

Nonsmoking after simultaneous alcohol abstinence and smoking cessation program was associated with better drinking status outcome in Japanese alcohol-dependent men: A prospective follow-up study.

BACKGROUND: Growing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians. METHOD: We prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation. RESULTS: Nonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge. CONCLUSION: Nonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs.

Influence of early-life adversity on responses to acute and chronic ethanol in female mice.

BACKGROUND: Stressful early-life experiences increase the risk of developing an alcohol use disorder. We previously found that male C57BL/6J mice reared under limited bedding and nesting (LBN) conditions, a model of early-life adversity, escalate their ethanol intake in limited-access two-bottle choice (2BC) sessions faster than control (CTL)-reared counterparts when exposed to chronic intermittent ethanol (CIE) vapor inhalation. However, the alcohol consumption of female littermates was not affected by LBN or CIE. In the present study, we sought to determine whether this phenotype reflected a general insensitivity of female mice to the influence of early-life stress on alcohol responses. METHODS: In a first experiment, CTL and LBN females with a history of 2BC combined or not with CIE were tested in affective and nociceptive assays during withdrawal. In a second group of CTL and LBN females, we examined ethanol-induced antinociception, sedation, plasma clearance, and c-Fos induction. RESULTS: In females withdrawn from chronic 2BC, CIE increased digging, reduced grooming, and increased immobility in the tail suspension test regardless of early-life history. In contrast, LBN rearing lowered mechanical nociceptive thresholds regardless of CIE exposure. In females acutely treated with ethanol, LBN rearing facilitated antinociception and delayed the onset of sedation without influencing ethanol clearance rate or c-Fos induction in the paraventricular nucleus of the hypothalamus, paraventricular nucleus of the thalamus, central nucleus of the amygdala, or auditory cortex. CONCLUSION: CIE withdrawal produced multiple indices of negative affect in C57BL/6J females, suggesting that their motivation to consume alcohol may differ from air-exposed counterparts despite equivalent intake. Contrasted with our previous findings in males, LBN-induced mechanical hyperalgesia in chronic alcohol drinkers was specific to females. Lower nociceptive thresholds combined with increased sensitivity to the acute antinociceptive effect of ethanol may contribute to reinforcing ethanol consumption in LBN females but are not sufficient to increase their intake.

Vivências e sentidos do uso prejudicial de álcool e outras drogas / Experiences and meanings of the harmful use of alcohol and other drugs / Experiencias y significados del consumo nocivo de alcohol y otras drogas

Objetivo: compreender os sentidos e as vivências de uso prejudicial de álcool e outras drogas, sob a ótica de usuários da Rede de Atenção Psicossocial. Método: estudo qualitativo, descritivo, exploratório, que entrevistou 13 participantes adultos nos meses de setembro a dezembro de 2019. A análise firmou-se nos aportes da análise de conteúdo temática de Bardin, resultando as categorias, perdas e fracasso na vida, culpa, dualismo vida e morte - das cinzas à fênix, recaída. Resultados: o uso de substâncias remete a perdas familiares, de moradia, trabalho, dignidade; a destruição, fracasso. A recaída denota falha, pecado; acarreta culpa, auto-estigma. O sofrimento trespassa as tentativas de buscar do cuidado; reverbera na perda do sentido da vida, no comportamento suicida ou na resiliência e esperança-equilibrista. Conclusão: a clínica ampliada deve valorizar a geografia afetiva dos usos e a redução de danos.

Objectives: to understand the meanings and experiences of harmful use of alcohol and other drugs, from the perspective of users of the Psychosocial Care Network. Method: qualitative, descriptive, exploratory study that interviewed 13 adult participants in the months from September to December 2019. The analysis was based on Bardin's thematic content analysis, resulting in the categories, loss and failure in life, guilt, life and death dualism - from ashes to phoenix, relapse. Results: substance use refers to loss of family, housing, work, dignity; destruction, failure. Relapse denotes failure, sin; it brings guilt, self-stigma. Suffering goes through the attempts to seek care; it reverberates in the loss of the meaning of life, suicidal behavior or resilience and hope-equilibrist. Conclusion: the expanded clinic must value the affective geography of uses and harm reduction.

Objetivos:comprender los significados y experiencias del uso nocivo de alcohol y otras drogas, desde la perspectiva de los usuarios de la Red de Atención Psicosocial. Método: estudio cualitativo, descriptivo, exploratorio, que entrevistó a 13 participantes adultos en los meses de septiembre a diciembre de 2019. El análisis se basó en el análisis de contenido temático de Bardin, resultando en las categorías, pérdida y fracaso en la vida, culpa, dualismo vida y muerte - de las cenizas al ave fénix, recaída. Resultados:el uso de sustancias se refiere a pérdidas familiares, vivienda, trabajo, dignidad; destrucción, fracaso. La recaída denota fracaso, pecado; conlleva culpa, autoestigma. El sufrimiento pasa por los intentos de buscar atención; reverbera en la pérdida del sentido de la vida, conducta suicida o resiliencia y esperanza-equilibrista. Conclusión: la clínica ampliada debe valorar la geografía afectiva de los usos y la reducción de daños.

Loneliness and Increased Hazardous Alcohol Use: Data from a Nationwide Internet Survey with 1-Year Follow-Up.

We aimed to examine the association between loneliness and developing alcohol dependence or hazardous alcohol use. A cohort study was conducted utilizing data from a nationwide internet survey in 2021 and 2022 in Japan. A total of 15,854 follow-up participants (55% men, with a mean age of 52.8 years) were divided based on AUDIT scores: nondrinkers (AUDIT: 0), low-risk drinkers (AUDIT: 1-7), medium-risk drinkers (AUD: 8-14), high-risk drinkers (AUDIT: 15-19), and probable alcohol dependence (AUDIT: 20-40). The University of California, Los Angeles Loneliness Scale (Version 3), a short-form three-item scale, was used to assess loneliness (high loneliness score of ≥6). The prevalence of high loneliness was higher in nondrinkers than that in low- and medium-risk drinkers, i.e., 22%, 18%, and 17%, respectively, as well as in high-risk drinkers (32%) and those with probable alcohol dependence (43%) compared to non-high-risk drinkers (19%). After adjusting for various factors (sociodemographic, social isolation, psychological distress, and smoking), non-high-risk drinkers (AUDIT: 0-14) with high loneliness were more likely to become high-or-over-risk drinkers (AUDIT: 15-40) than those without high loneliness, with adjusted risk ratios of 1.45 (95% confidence interval: 1.08-1.96) through multivariable binary logistic regression. Among non-high-risk drinkers, people with high loneliness scores at baseline were associated with increased high-risk drinking patterns with probable alcohol dependence.

Protocol for an RCT on cognitive bias modification for alcohol use disorders in a religion-based rehabilitation program.

INTRODUCTION: Alcohol-related cues trigger relapse in patients with alcohol use disorders (AUDs). These cues may automatically activate motivational approach tendencies. Through computerised cognitive bias modification (CBM), the tendencies of patients with AUD to approach alcohol can be reduced. The present protocol describes a training intervention with approach bias modification (ApBM) incorporating religion-related stimuli as an alternative to alcohol to improve the effectiveness of CBM in a religion-based rehabilitation centre. AUD is often related to patients' religious attitudes in this treatment context. The religion-adapted ApBM, therefore, combines training in avoidance of alcohol-related motivational cues and an approach to religion-based motivational cues. This combination's effectiveness will be compared with a standard ApBM and to a sham ApBM. METHODS AND ANALYSIS: Using a double-blind multiarm parallel randomised controlled trial procedure (ratio 1:1:1), 120 patients with AUD will be randomised into 1 of 3 conditions (religion-adapted ApBM, standard ApBM or sham ApBM) with personalised stimuli. The interventions are delivered over 4 consecutive days during an inpatient detoxification programme in addition to treatment as usual. Assessments occur before the start of the training and after the fourth training session, with follow-up assessments after 1 and 4 months. A multivariate analysis of variance will be used with the primary outcomes, the percentage of days abstinent and meaning in life 4-month follow-up. Secondary outcomes include differences in reported training satisfaction and symptoms of AUD. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Medical Research Ethics Committee Academic Medical Center Amsterdam (Reference number: 2020_251). Further, study results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NL75499.018.20.

Active Cigarette Smoking Is Associated With Increased Age-Related Decline on Measures of Visuospatial Learning and Memory and Executive Function in Alcohol Use Disorder.

AIMS: The goal of this study was to determine if active cigarette smoking in Veterans with alcohol use disorder (AUD) was associated with greater age-related neurocognitive decline. METHODS: Veterans with AUD, in residential treatment (n = 125; 47 ± 14 years of age, min = 24, max = 76, 29 ± 26 days of abstinence), completed measures of executive functions, learning and memory, processing speed and working memory. Actively smoking AUD (AsAUD, n = 47) were active daily cigarette smokers; former smoking AUD (FsAUD, n = 45) were predominately daily smokers prior to study but did not smoke at the time of study; non-smoking AUD (NsAUD, n = 33) never used cigarettes or smoked 'only a few times' during lifetime. RESULTS: AsAUD demonstrated greater age-related decline on measures of visuospatial learning and memory, and response inhibition/cognitive flexibility, primarily relative to NsAUD; there were no age-related differences between FsAUD and NsAUD on any measure. There were few significant mean differences between groups across the 15 neurocognitive measures. In AsAUD, higher scores on indices of smoking severity were associated with poorer performance on measures of auditory-verbal learning and memory, response inhibition, set-shifting and working memory. In FsAUD, longer smoking cessation duration was related to lower PTSD, anxiety and depressive symptomatology. CONCLUSIONS: Active smoking was associated with accelerated age-related decline on cognitive functions implicated in response to common evidence-based AUD interventions. Results suggest that smoking history contributes to the considerable heterogeneity observed in neurocognitive function in early AUD recovery, and reinforce the clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

Alcohol use disorder, psychiatric comorbidities, marriage and divorce in a high-risk sample.

OBJECTIVE: To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. METHOD: Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ∼ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. RESULTS: Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70-0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66-0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, ps < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59-2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. CONCLUSIONS: In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder-Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial.

INTRODUCTION: Although alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a certain extent, new approaches are needed to complement these pharmaca. One potential compound is oxytocin (OXY), which proved beneficial effects on alcohol craving and stress reactivity in preliminary clinical studies and synergism with NTX effects. METHODS AND ANALYSIS: This clinical phase II trial is a monocentre two-armed, placebo (PLC)-controlled, 1:1 randomised, double-blind, parallel-group study. 62 participants with AD will be randomised to receive either intranasal OXY spray (24 IU) or PLC spray plus oral NTX (50 mg) for 2 days, and alcohol craving will be assessed using a validated combined stress-exposure and cue-exposure experiments and MRI. The primary outcome will be the intensity of alcohol craving, assessed using the Alcohol Urge Questionnaire (AUQ), 60 min after OXY/PLC application, directly after the stress and cue exposures. Secondary outcomes include subjective stress, negative affect, cortisol and OXY plasma levels, and neural response to alcohol and emotional cues and natural rewards. Follow-up drinking data were collected over 90 days. The primary efficacy analysis will test the difference between the verum and the PLC group in the distribution of AUQ craving scores. Appropriate statistical analysis will be used for the evaluation of the secondary outcomes. ETHICS AND DISSEMINATION: This trial has been approved by the ethics committee of Heidelberg University and competent authority. All participants in the trial will provide written informed consent. The study will be conducted according to the principles of the Declaration of Helsinki and in accordance to the German Medicinal Products act. Results of this study will be disseminated in peer-reviewed scientific journals and deidentified data, and the statistical analysis plan will be made available via open-access online repositories. TRIAL REGISTRATION NUMBERS: EudraCT 2021-003610-40 and NCT05093296.

Mental health-related quality of life by sex and sexual identity among U.S. adults with alcohol and tobacco use disorder.

INTRODUCTION: Alcohol use disorder (AUD) and tobacco use disorder (TUD) are more severe among some sexual minority subgroups. It is less understood whether mental health indicators also differ by sexual identity among those with more severe forms of AUD and TUD. We examined differences in mental health-related QoL by sex-specific sexual identity subgroup among those meeting criteria for moderate-to-severe AUD or moderate-to-severe TUD. METHODS: We analyzed data from the National Epidemiologic Study of Alcohol and Related Conditions-III (2012-2013; n = 36,309). Our analyses focused on those meeting criteria for past-year moderate-to-severe AUD (n = 2341) and past-year moderate-to-severe TUD (n = 3675). Using multivariable linear regression, we examined associations of sex-specific sexual identity subgroups with mental health-related QoL, while controlling for (a) sociodemographic characteristics, (b) disorder severity, and (c) risk and protective factors (adverse childhood experiences, parental history of substance misuse, stressful life events, and social support). RESULTS: Among those with past-year moderate-to-severe AUD, gay men and heterosexual, bisexual, and gay/lesbian women had significantly lower mental health-related QoL compared to heterosexual men in fully adjusted models. Among those with past-year moderate-to-severe TUD, gay men and heterosexual and gay/lesbian women had significantly lower mental health-related QoL compared to heterosexual women. Bisexual and heterosexual women were not significantly different in fully adjusted models. DISCUSSION: Clinicians should consider the variability in mental health-related QoL among those with moderate-to-severe AUD and TUD particularly for women and sexual minorities. Consideration of current and past stressors and the degree of social support may be beneficial when conducting assessments and forming treatment plans.

Acute and chronic ethanol administration: A potential model of behavioral sensitization using wheel-running in male CD1 mice.

RATIONALE: We define behavioral sensitization as an augmented response to subsequent dosing after chronic intermittent administration of a drug. However, the biphasic effects of ethanol (EtOH), first stimulatory followed by depressive, make animal models of behavioral sensitization rare. OBJECTIVES: This study aimed to determine a dose of EtOH that did not depress wheel-running (WR) in CD1 mice and then to develop a model of EtOH-induced behavioral sensitization. METHODS: For the first part of this study, male CD1 mice (n = 24, 6/group) were administered either phosphate buffer saline (PBS), 0.5 g/kg, 1 g/kg, or 2 g/kg EtOH at a volume of 3 ml/kg, intraperitoneally (IP). Mice were divided into equal groups and received the weight-based dose once daily on Days 1, 2, 3, 4, and 5. All mice received a challenge dose of 0.5 g/kg on Day 10. In both parts of the study, mice were habituated to the running wheel for 5 min prior to dosing and wheel running was measured for 10 min after each dose. RESULTS: The acute dose-response of EtOH effects on wheel running determined a significant difference between doses in wheel running (p < 0.05), with a post-hoc analysis establishing that 0.5 g/kg EtOH resulted in significantly more WR compared to 2 g/kg EtOH (p < 0.05). The chronic study demonstrated a significant main effect of Day (1 vs. 5 vs. Challenge, p < 0.001) and an interaction between Day and Treatment, with post-hoc analysis determining the effect to be between PBS and EtOH WR on Day 5 (p < 0.05). In addition, Bonferroni post-hoc analysis determined no differences between Days in the PBS condition, but a significant difference in the EtOH condition between Day 1 and Day 5 (p < 0.001) and that difference from Day 1 persisted when comparing to the Challenge Day (p < 0.01). CONCLUSION: After chronic, intermittent, low dose administration of EtOH, male mice showed an increase in activity as measured by wheel running. Therefore, we laid the groundwork for a potentially useful rodent model for EtOH-induced behavioral sensitization.

Topiramate decreases the salience of motivationally relevant visual cues among smokers with alcohol use disorder.

BACKGROUND: There is preliminary evidence that the anticonvulsant topiramate increases the likelihood of both smoking and alcohol abstinence among smokers with alcohol use disorder (AUD), but its therapeutic mechanism has not been determined. We used event-related potentials (ERPs) to evaluate topiramate's effect on the salience of drug-related, emotional, and neutral pictorial cues to identify whether one of its potential therapeutic mechanisms involves reduction of the salience of motivationally relevant cues. METHODS: Participants enrolled in a multisite clinical trial treating smokers with AUD were randomly assigned to receive placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day), along with brief behavioral compliance enhancement treatment. A subsample (n = 101) completed ERP assessments at baseline (1 week pre-medication) and week 5 (5 weeks on medication; 1 week pre-quit). We assessed the salience of pleasant, unpleasant, cigarette-related, alcohol-related, and neutral pictorial cues using the late positive potential (LPP) ERP component and measured self-reported substance use, reinforcement, craving, and withdrawal. RESULTS: Five weeks of high-dose topiramate treatment decreased LPP amplitudes in response to both emotional (pleasant and unpleasant) and drug-related cues (alcohol and cigarette), but not to neutral cues. However, results showed that the LPPs were not significant mediators of the relationship between topiramate dose and post-quit measures of substance use, reinforcement, craving, or withdrawal. CONCLUSIONS: These findings suggest that high-dose topiramate (up to 250 mg/day) decreases the motivational salience of both drug-related and emotional cues among smokers with AUD. However, the nonsignificant mediation analyses preclude any firm conclusions about whether this effect represents one of topiramate's therapeutic mechanisms of action.

The phenotype of recovery VI: The association between life-history strategies, delay discounting, and maladaptive health and financial behaviors among individuals in recovery from alcohol use disorders.

BACKGROUND: The life-history theory is a well-established framework that predicts behaviors and explains how and why organisms allocate effort and resources to different life goals. Delay discounting (DD) is associated with risky behaviors and has been suggested as a candidate behavioral marker of addiction. Thus, we investigated the relationship between DD, life-history strategies, and engagement in risky behaviors among individuals in recovery from alcohol use disorder (AUD). METHODS: Data from 110 individuals in recovery from addiction from The International Quit & Recovery Registry, an ongoing online registry designed to understand recovery phenotype, were included in the analysis. The association between life-history strategies, DD, engagement in risky behaviors, and remission status were assessed. RESULTS: Life-history strategy scores were significantly associated with DD rates and finance, health, and personal development behaviors after controlling for age, sex, race, ethnicity, years of education, marital status, smoking status, and history of other substance use. Remission status was significantly associated with life-history strategy, DD, drug use, fitness, health, and safe driving after controlling for age, sex, race, years of education, marital status, and smoking status. In addition, a mediation analysis using Hayes' methods revealed that the discounting rates partially mediated the association between remission status and life-history strategy scores. CONCLUSIONS: Life-history strategies and remission status are both significantly associated with DD and various health and finance behaviors among individuals in recovery from AUD. This finding supports the characterizations of DD as a candidate behavioral marker of addiction that could help differentiate subgroups needing special attention or specific interventions to improve the outcomes of their recovery. Future longitudinal studies are warranted to understand the relationships between changes in life-history strategies, DD, maladaptive health behaviors, and remission status over time.