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Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction.

AbstractObjectiveTo evaluate the effectiveness of a doctor delivered screening and ultra-brief intervention (<1 minute) compared with simplified assessment only for reducing alcohol intake among patients with hazardous drinking in primary care.DesignPragmatic cluster randomised controlled trial.Setting40 primary care clinics in Japan that did not provide routine screening and brief intervention for hazardous drinking or treatment or self-help groups for alcohol dependency.Participants1133 outpatients aged 20-74 years with hazardous drinking (AUDIT-C (alcohol use disorders identification test-consumption) scores ≥5 for men and ≥4 for women). Clinic clusters were allocated to a study arm using a computer generated random sequence. Participants and staff who collected participant reported outcomes remained blinded to assignment.InterventionsPrimary care clinics were randomised to ultra-brief intervention (21 clinics, 531 patients) or simplified assessment only (19 clinics, 602 patients) groups. The intervention group comprised screening with AUDIT-C followed by brief oral advice and an alcohol information leaflet delivered in <1 minute. The control group comprised simplified assessment with AUDIT-C only.Main outcome measuresThe primary outcome was total alcohol consumption in the four weeks preceding the 24 week follow-up. Secondary outcomes included total alcohol consumption in the four weeks preceding the 12 week follow-up, and readiness to change drinking behaviour, measured at 12 and 24 weeks.ResultsAt 24 weeks, the difference in total alcohol consumption between the ultra-brief intervention group (1046.9 g/4 weeks (g/4wk), 95% confidence interval (CI) 918.3 to 1175.4) and control group (1019.0 g/4wk, 893.5 to 1144.6) was 27.8 g/4wk (−149.7 to 205.4, P=0.75), with a Hedges’ g of 0.02 (95% CI −0.10 to 0.14). At 12 weeks, the difference in total alcohol consumption between the intervention group (1034.1 g/4wk, 919.6 to 1148.7) and control group (979.3 g/4wk, 866.1 to 1092.4) was 54.9 g/4wk (−104.1 to 213.9, P=0.49), with a Hedges’ g of 0.04 (−0.08 to 0.16).ConclusionThis trial found no evidence to support the effectiveness of a doctor delivered ultra-brief intervention for hazardous drinking compared with simplified assessment only in primary care in Japan.Trial registrationUMIN Clinical Trials Registry UMIN000051388.

Alcohol use contributes to over 3 million deaths annually. In Tanzania, there are no evidence-based culturally adapted interventions to address harmful alcohol use behaviors. Our hypothesis was that \"Punguza Pombe Kwa Afya Yako\" (PPKAY, Reduce Alcohol for your Health), a culturally adapted brief intervention with text-based boosters, is superior to usual care in reducing binge drinking at 3 months post discharge. This manuscript reports. Stage 1 of our adaptive clinical trial which seeks to determine the effectiveness of the PPKAY+ booster to usual care; a subsequent stage will compare the PPKAY only to personalized and standard boosters. Adults who sought care for an acute injury at the Kilimanjaro Christian Medical Centre Emergency Department, self-disclosed alcohol use prior to the injury, scored ≥8 on the Alcohol Use Disorder Identification Test, and/or test positive by alcohol breathalyzer were offered enrollment. Participants were randomly assigned to PPKAY+ boosters (personalized or standard) or usual care at 1:1:1 allocation. Primary analyses followed the intention-to-treat principle. The PPKAY is a 15-min nurse delivered brief intervention using motivational interviewing techniques combined with a standardized or personalized text based reminder sent weekly to participants after hospital discharge and until 1 year post enrollment compared to a usual care arm. Follow-up was performed by blinded outcome assessors. Our pooled intervention arms PPKAY+ boosters were compared to usual care to determine the effectiveness of the intervention in reducing the number of binge drinking days, the trial's primary outcome, in the previous 4 weeks at 3 months after discharge. A total of 1,484 patients were screened for eligibility between October 12th 2020, and on April 14th 2023. 448 patients met inclusion criteria and consented to participate. 148 were randomized to usual care, and 300 to the pooled intervention arm. Reasons for attrition included loss to follow-up (n = 69), withdrawal (n = 6), and deaths (n = 4), with no differences between arms. Most participants were male (94%), from the Chagga tribe (59%) and had an average age of 36.4 years (SD 12.6) at baseline. At the 3-month follow-up, the intervention arm showed a notable reduction in mean predicted binge drinking days by 1.2 days (95% CI: [-2.3, -0.3]; p = 0.002) compared to the usual care group in a difference-in-differences analysis. Importantly, the self-reported nature of our primary outcome introduces the potential for social desirability bias, particularly in the absence of participant blinding, and should be considered a limitation when interpreting the findings. The reduction in binge drinking behavior at 3-month follow-up compared to usual care suggests our culturally adapted intervention is an effective alcohol intervention for patients acutely injured in Tanzania. According to the adaptive study design, the next phases of the trial will continue to compare the intervention arm with a paired down version without the text messages boosters. ClinicalTrials.gov NCT04535011.

Objective To evaluate the effectiveness of different brief intervention strategies at reducing hazardous or harmful drinking in primary care. The hypothesis was that more intensive intervention would result in a greater reduction in hazardous or harmful drinking.Design Pragmatic cluster randomised controlled trial.Setting Primary care practices in the north east and south east of England and in London.Participants 3562 patients aged 18 or more routinely presenting in primary care, of whom 2991 (84.0%) were eligible to enter the trial: 900 (30.1%) screened positive for hazardous or harmful drinking and 756 (84.0%) received a brief intervention. The sample was predominantly male (62%) and white (92%), and 34% were current smokers.Interventions Practices were randomised to three interventions, each of which built on the previous one: a patient information leaflet control group, five minutes of structured brief advice, and 20 minutes of brief lifestyle counselling. Delivery of the patient leaflet and brief advice occurred directly after screening and brief lifestyle counselling in a subsequent consultation.Main outcome measures The primary outcome was patients’ self reported hazardous or harmful drinking status as measured by the alcohol use disorders identification test (AUDIT) at six months. A negative AUDIT result (score <8) indicated non-hazardous or non-harmful drinking. Secondary outcomes were a negative AUDIT result at 12 months, experience of alcohol related problems (alcohol problems questionnaire), health utility (EQ-5D), service utilisation, and patients’ motivation to change drinking behaviour (readiness to change) as measured by a modified readiness ruler.Results Patient follow-up rates were 83% at six months (n=644) and 79% at 12 months (n=617). At both time points an intention to treat analysis found no significant differences in AUDIT negative status between the three interventions. Compared with the patient information leaflet group, the odds ratio of having a negative AUDIT result for brief advice was 0.85 (95% confidence interval 0.52 to 1.39) and for brief lifestyle counselling was 0.78 (0.48 to 1.25). A per protocol analysis confirmed these findings.Conclusions All patients received simple feedback on their screening outcome. Beyond this input, however, evidence that brief advice or brief lifestyle counselling provided important additional benefit in reducing hazardous or harmful drinking compared with the patient information leaflet was lacking.Trial registration Current Controlled Trials ISRCTN06145674.

Alcohol abuse disrupts core executive functions, including working memory (WM)—the ability to maintain and manipulate goal-relevant information. When executive functions like WM are weakened, drinking behavior gets out of control and is guided more strongly by automatic impulses. This study investigated whether training WM restores control over drinking behavior. Forty-eight problem drinkers performed WM training tasks or control tasks during 25 sessions over at least 25 days. Before and after training, we measured WM and drinking behavior. Training WM improved WM and reduced alcohol intake for more than 1 month after the training. Further, the indirect effect of training on alcohol use through improved WM was moderated by participants' levels of automatic impulses: Increased WM reduced alcohol consumption in participants with relatively strong automatic preferences for alcohol. These findings are consistent with the theoretical framework and demonstrate that training WM may be an effective strategy to reduce alcohol use by increasing control over automatic impulses to drink alcohol.

Modifying behaviors, such as alcohol consumption, is difficult. Creating psychological distance between unhealthy triggers and one’s present experience can encourage change. Using two multisite, randomized experiments, we examine whether theory-driven strategies to create psychological distance—mindfulness and perspective-taking—can change drinking behaviors among young adults without alcohol dependence via a 28-day smartphone intervention (Study 1, N  = 108 participants, 5492 observations; Study 2, N  = 218 participants, 9994 observations). Study 2 presents a close replication with a fully remote delivery during the COVID-19 pandemic. During weeks when they received twice-a-day intervention reminders, individuals in the distancing interventions reported drinking less frequently than on control weeks—directionally in Study 1, and significantly in Study 2. Intervention reminders reduced drinking frequency but did not impact amount. We find that smartphone-based mindfulness and perspective-taking interventions, aimed to create psychological distance, can change behavior. This approach requires repeated reminders, which can be delivered via smartphones.

This study examined the impact of the Family Check-Up (FCU) and linked intervention services on reducing health-risk behaviors and promoting social adaptation among middle school youth. A total of 593 students and their families were randomly assigned to receive either the intervention or middle school services as usual. Forty-two percent of intervention families engaged in the service and received the FCU. Using complier average causal effect analyses, engagement in the intervention moderated intervention outcomes. Families who engaged in the intervention had youth who reported lower rates of antisocial behavior and substance use over time than did a matched control sample. Results extend previous research indicating that a family-centered approach to supporting youth in the public school setting reduced the growth of antisocial behavior, alcohol use, tobacco use, and marijuana use throughout the middle school years.

Rationale Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR α4β2 subunit partial agonist varenicline (Chantix™), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518–12523, 2007 ) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655–663, 2011 ; McKee et al., Biol Psychiatry 66:185–190 2009 ). Objectives We present a randomized, double-blind, 16-week study in heavy-drinking smokers ( n  = 64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens. Results Varenicline significantly decreases alcohol consumption ( χ 2  = 35.32, p  < 0.0001) in smokers. Although varenicline has previously been associated with suicidality and depression, side effects were low in this study and declined over time in the varenicline treatment group. Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.