The effects of acute oral naltrexone pretreatment on the abuse potential of intranasal methamphetamine, and the relationship between reward/punishment sensitivity and methamphetamine's effects.

One potential medication for treating methamphetamine use disorder is the opioid antagonist naltrexone (NLTX). Despite encouraging preclinical findings, the results of clinical studies have been mixed. The primary aim of the current trial was to examine the effects of acute NLTX pretreatment on the subjective and reinforcing effects of intranasal methamphetamine. Nonmedical psychostimulant users completed outpatient testing sessions in which they received oral placebo (0 mg) or NLTX (50 mg) before intranasal methamphetamine (30 mg/70 kg). Primary outcome measures were peak positive subjective effects (e.g. drug 'Liking') assessed on a visual analog scale (0-100), and methamphetamine self-administration using an operant self-administration task. Participants also completed a probabilistic categorization task to assess reward and punishment learning sensitivity. Complete data were available from 13 male and 1 transgender (male-to-female) participant (age: 33.4 ± 7.6 years). Intranasal methamphetamine significantly increased subjective ratings of drug 'Liking', 'Good Effect' and 'High' from baseline (P's < 0.01), but did not significantly vary as a function of placebo or NLTX pretreatment. Similarly, methamphetamine self-administration did not vary between the placebo and NLTX pretreatment conditions. This sample did not demonstrate a significant 'bias' in learning from positive and negative outcomes (i.e. reward and punishment sensitivity), and reward/punishment sensitivity was not correlated with the effects of methamphetamine or the effects of NLTX on methamphetamine. The current study argues against the use of NLTX as a stand-alone medication for treating methamphetamine use disorder.

Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HT1A PET.

BACKGROUND: Lithium, one of the few effective treatments for bipolar depression (BPD), has been hypothesized to work by enhancing serotonergic transmission. Despite preclinical evidence, it is unknown whether lithium acts via the serotonergic system. Here we examined the potential of serotonin transporter (5-HTT) or serotonin 1A receptor (5-HT1A) pre-treatment binding to predict lithium treatment response and remission. We hypothesized that lower pre-treatment 5-HTT and higher pre-treatment 5-HT1A binding would predict better clinical response. Additional analyses investigated group differences between BPD and healthy controls and the relationship between change in binding pre- to post-treatment and clinical response. Twenty-seven medication-free patients with BPD currently in a depressive episode received positron emission tomography (PET) scans using 5-HTT tracer [11C]DASB, a subset also received a PET scan using 5-HT1A tracer [11C]-CUMI-101 before and after 8 weeks of lithium monotherapy. Metabolite-corrected arterial input functions were used to estimate binding potential, proportional to receptor availability. Fourteen patients with BPD with both [11C]DASB and [11C]-CUMI-101 pre-treatment scans and 8 weeks of post-treatment clinical scores were included in the prediction analysis examining the potential of either pre-treatment 5-HTT or 5-HT1A or the combination of both to predict post-treatment clinical scores. RESULTS: We found lower pre-treatment 5-HTT binding (p = 0.003) and lower 5-HT1A binding (p = 0.035) were both significantly associated with improved clinical response. Pre-treatment 5-HTT predicted remission with 71% accuracy (77% specificity, 60% sensitivity), while 5-HT1A binding was able to predict remission with 85% accuracy (87% sensitivity, 80% specificity). The combined prediction analysis using both 5-HTT and 5-HT1A was able to predict remission with 84.6% accuracy (87.5% specificity, 60% sensitivity). Additional analyses BPD and controls pre- or post-treatment, and the change in binding were not significant and unrelated to treatment response (p > 0.05). CONCLUSIONS: Our findings suggest that while lithium may not act directly via 5-HTT or 5-HT1A to ameliorate depressive symptoms, pre-treatment binding may be a potential biomarker for successful treatment of BPD with lithium. CLINICAL TRIAL REGISTRATION: PET and MRI Brain Imaging of Bipolar Disorder Identifier: NCT01880957; URL: https://clinicaltrials.gov/ct2/show/NCT01880957.

Social motivational processing and interpersonal function in aging cocaine smokers.

Illicit drug use among aging cohorts is increasing, yet little is known about functional impairments in older drug users. Given the importance of social integration for aging and documented social decrements in cocaine users, we examined social function and its neurocognitive substrates in aging cocaine users relative to carefully matched non-cocaine users. Regular (≥twice/week), long-term (≥15 years) cocaine smokers 50-60 years old (COCs; n = 22; four women) and controls (CTRLs; n = 19; four women) underwent standardized probes of social reward and threat processing during functional magnetic resonance imaging and a behavioral facial affect recognition task. Self-report and peer-report of daily interpersonal function were also collected. COCs, and CTRLs reporting current marijuana or alcohol use, were tested after four drug-free inpatient days. COCs had pronounced problems in daily social function relative to CTRLs indicated by both their own and their peers' reports. Compared with CTRLs, COCs had stronger amygdala responses to social threat versus control stimuli, with no other differences in social processing or cognition. Aging cocaine users appear to have marked, generalized difficulties in 'real-world' interpersonal function but largely intact social processing on laboratory-based measures when compared with appropriately matched controls and tested under well-controlled conditions. Daily social difficulties may be related to transient factors such as acute/residual drug effects or cocaine-related changes in health behaviors (e.g. disrupted sleep and poor diet). These data suggest that interpersonal function may be a valid intervention target for aging cocaine users and warrants further study in older drug users.

Understanding and shifting drug-related decisions: contributions of automatic decision-making processes.

While substance use is common, only a minority of individuals who use drugs or alcohol develop problematic use. An understanding of the factors underlying the transition from substance use to misuse may improve prevention and intervention efforts. A key feature of substance misuse is ongoing decisions to use drugs or alcohol despite escalating negative consequences. Research findings highlight the importance of both relatively automatic, associative cognitive processes and relatively controlled, deliberative, and rational-analytic cognitive processes, for understanding situational decisions to use drugs. In this review, we discuss several cognitive component processes that may contribute to decision-making that promotes substance use and misuse, with a focus on more automatic processes. A growing body of evidence indicates that relative differences in the strength of these component processes can account for individual differences in the transition from substance use to misuse and may offer important avenues for developing novel intervention strategies.

Verbal learning in marijuana users seeking treatment: a comparison between depressed and non-depressed samples.

BACKGROUND: Both individuals with marijuana use and depressive disorders exhibit verbal learning and memory decrements. OBJECTIVES: This study investigated the interaction between marijuana dependence and depression on learning and memory performance. METHODS: The California Verbal Learning Test-Second Edition (CVLT-II) was administered to depressed (n = 71) and non-depressed (n = 131) near-daily marijuana users. The severity of depressive symptoms was measured by the self-rated Beck Depression Inventory (BDI-II) and the clinician-rated Hamilton Depression Rating Scale (HAM-D). Multivariate analyses of covariance statistics (MANCOVA) were employed to analyze group differences in cognitive performance. Pearson's correlation coefficients were calculated to examine the relative associations between marijuana use, depression and CVLT-II performance. Findings from each group were compared to published normative data. RESULTS: Although both groups exhibited decreased CVLT-II performance relative to the test's normative sample (p < 0.05), marijuana-dependent subjects with a depressive disorder did not perform differently than marijuana-dependent subjects without a depressive disorder (p > 0.05). Further, poorer CVLT-II performance was modestly associated with increased self-reported daily amount of marijuana use (corrected p < 0.002), but was not significantly associated with increased scores on measures of depressive symptoms (corrected p > 0.002). CONCLUSION: These findings suggest an inverse association between marijuana use and verbal learning function, but not between depression and verbal learning function in regular marijuana users.

An Implementation Approach to Translating Assessment Data into Treatment for Disorders of Addiction.

Effective translation of data to inform real-time patient care is lacking in addiction inpatient settings. The current study presents the optimization of an assessment report that is used by clinicians to individualize treatment. A multi-aim, iterative approach was taken, utilizing an implementation science perspective to arrive at a final version of the assessment report. This occurred at a small inpatient addiction treatment facility. Participants were all available clinical staff (N = 7; female = 71%). A quantitative survey was used for aims 1 and 2 to, respectively, assess motives and context around the report as well as evaluate its design. Aim 3 focused on optimization via semi-structured interviews. Descriptive and modified content analyses were utilized appropriately across aims. This resulted in five versions of the assessment report being created between February 2021 and August 2022, the most recent of which was adapted into patients' electronic medical records. We discuss each version of the report in depth, including clinicians' iterative feedback and researchers' perceived barriers to this translational process. The response rate was 64.3%. The current study highlights a replicable approach for optimizing the translation of assessment data into treatment for patients with disorders of addiction as well as an assessment report that could be utilized by similar facilities with a naturally low sample size.

Automated, tailored adaptive mobile messaging to reduce alcohol consumption in help-seeking adults: A randomized controlled trial.

AIMS: To test differential outcomes between three 6-month text-messaging interventions to reduce at-risk drinking in help-seeking adults. DESIGN: A three-arm single-blind randomized controlled trial with 1-, 3-, 6- and 12-month follow-ups. SETTING: United States. A fully remote trial without human contact, with participants recruited primarily via social media outlets. PARTICIPANTS: Seven hundred and twenty-three adults (mean = 39.9 years, standard deviation = 10.0; 62.5% female) seeking to reduce their drinking were allocated to 6 months of baseline 'tailored statically' messaging (TS; n = 240), 'tailored adaptive' messaging (TA; n = 239) or 'drink tracking' messaging (DT; n = 244). INTERVENTIONS: TS consisted of daily text messages to reduce harmful drinking that were tailored to demographics and alcohol use. TA consisted of daily, tailored text messages that were also adapted based on goal achievement and proactive prompts. DT consisted of a weekly assessment for self-reported drinking over the past 7 days. MEASUREMENTS: The primary outcome measure was weekly sum of standard drinks (SSD) at 6-month follow-up. Secondary outcome measures included drinks per drinking day (DDD), number of drinking days (NDD) per week and heavy drinking days (HDD) at 1-, 3-, 6- and 12-month follow-ups. FINDINGS: At 6 months, compared with DT, TA resulted in significant SSD reductions of 16.2 (from 28.7 to 12.5) drinks [adjusted risk ratio (aRR) = 0.80, 95% confidence interval (CI) = 0.71, 0.91] using intent-to-treat analysis. TA also resulted in significant improvements in DDD (aRR = 0.84; 95% CI = 0.77-0.92) and drinking days per week (b = -0.39; 95% CI = -0.67, -0.10), but not HDD compared with DT at 6 months. TA was not significantly different from TS at any time-point, except DDD at 6 months. All groups made improvements in SSD at 12-month follow-up compared with baseline with an average reduction of 12.9 drinks per week across groups. CONCLUSIONS: Automated tailored mobile messaging interventions are scalable solutions that can reduce weekly alcohol consumption in remote help-seeking drinkers over time.

Adapting, Implementing, and Maintaining a Group Cognitive Behavioral Therapy Program at an Inpatient Addiction Treatment Facility.

Background: Quality training is an oft-cited barrier to effective implementation and ongoing delivery of high-quality evidence-based practice (EBP) across fields. This is especially true in the addiction field, but there is little cited evidence for optimal methods to improve EBP in inpatient addiction facilities with minimal resources. Objective: The current paper focuses on evaluating the state of our facility's group CBT manual and clinical training on the manual in a "realistic" (ie, non-RCT, non-grant-funded) inpatient addiction treatment setting. Methods: Five full-time clinicians volunteered to take part in the study (woman = 60%; Mage = 36.20 years). The study involved a mix of semi-structured interviews and surveys designed to measure seven outcomes (barriers, feasibility, useability, appropriateness, acceptability, burden, trialability). Results: Three themes emerged from the data that impacted the group CBT manual: training, timing, and functionality. Addressing these themes allowed for a new, optimal manual and training procedure to be put into place. Conclusion: The current study highlights that under-resourced inpatient addiction facilities can still methodically utilize implementation approaches to study their EBP, namely CBT. Such an approach will ensure that the highest quality care is being delivered to patients and actively addresses known training barriers that prevent proper EBP delivery.

Measures of attentional bias and relational responding are associated with behavioral treatment outcome for cocaine dependence.

BACKGROUND: Psychosocial interventions for substance dependence have demonstrated efficacy. However, the mechanisms by which specific intervention strategies exert their effect have not been clearly identified. OBJECTIVE: This study investigated the prospective relationships between two psychological processes, an attentional bias toward cocaine stimuli and beliefs about the consequences of cocaine use, and treatment outcome. METHOD: Twenty-five cocaine-dependent participants enrolled in a 6-month outpatient treatment program that included voucher incentives for abstinence. All participants were asked to complete two implicit assessment procedures, a Drug Stroop protocol and an Implicit Relational Assessment Procedure (IRAP), as well as explicit measures of cocaine craving and the consequences of cocaine use, prior to beginning treatment. Pearson's correlation coefficients tested the prospective relationships between treatment outcome and the implicit and explicit assessments. RESULTS: Stronger implicit beliefs about the positive effects of cocaine use prior to treatment were associated with poorer treatment outcome when an escalating voucher-incentive program was in place. Further, an attentional bias for cocaine-related stimuli was associated with better treatment outcome when an escalating voucher-incentive program was removed. No association between cocaine use beliefs and treatment outcome was found when beliefs were measured with self-report instruments. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These findings highlight the potential utility of performance-based measures for delineating the psychological mechanisms associated with variation in response to treatment for drug dependence.

A pilot study comparing in-person and remote outpatient substance use treatment services on quality-of-life outcomes.

Background: The widespread shift from in-person to Telehealth services during the Covid-19 pandemic irreversibly shifted the landscape of outpatient substance use treatment. This shift was necessitated by health, rather than data-driven, reasons. As we reflect on whether to continue providing Telehealth services moving forward, we require empirical support on the effectiveness of Telehealth services (compared to in-person services) in terms of patient outcomes, such as Quality of Life (QOL), to support this decision. Objective: To present data from a pilot project comparing changes in QOL across patients receiving outpatient in-person versus Telehealth substance use treatment in five clinics across New York State. Method: To retrospectively compare total self-reported QOL scores from admission to 3-months later utilizing the Quality-of-Life Enjoyment and Satisfaction scale during in-person (pre-pandemic, n = 298) and Telehealth (pandemic, n = 316) services with a mixed repeated measures ANOVA. Results: Self-reported QOL scores significantly improved across the first three months, regardless of treatment modality. Conclusion: Telehealth and in-person treatment appear comparable on QOL outcomes over the first 3 months of outpatient treatment. Both modalities are associated with improved QOL scores. Scientific significance: These preliminary findings provide evidence that Telehealth services are associated with positive patient outcomes and appear comparable to QOL outcomes among patients receiving in-person services. Future directions include further assessment of additional clinical outcomes and investigation into causal mechanisms.

The Role of Daily Goal Setting Among Individuals with Alcohol Use Disorder.

Introduction: Individuals with alcohol use disorder (AUD) who seek help to reduce their drinking are expected to vary with respect to drinking goal, with some choosing abstinence and others moderation. The present research explored whether drinking goals vary day to day among individuals with AUD planning to enter treatment and the relationship of specific daily goals to actual drinking behavior in daily life. Methods: Participants were 153 individuals with AUD who enrolled in a study of stepped care brief interventions and completed smartphone momentary assessments in daily life. Drinking goals and number of standard drinks consumed were reported daily for 21 consecutive days after receiving brief advice but prior to assignment to further treatment. Daily drinking goals were coded as (a) complete abstinence (b) moderation, i.e., 2 or fewer standard drinks, or (c) other. Mixed-effects models nested daily drinking goals within individuals to consider both individual and daily patterns in daily goal setting. Results: Complete abstinence was the most common daily drinking goal and showed greater day-to-day stability than setting a moderation goal. Setting an abstinence goal in the morning was also most successful in limiting alcohol consumption later that day, relative to other goals. Those individuals who set more abstinence goals, however, were also those who drank more per drinking occasion. Conclusions: Findings support the clinical benefit of mapping daily goal setting and strategizing for specific circumstances. Future research may track the relation of daily drinking goals to successful goal achievement during treatment and compare to overall treatment goals.

MDMA for the Treatment of Negative Symptoms in Schizophrenia.

The profound economic burden of schizophrenia is due, in part, to the negative symptoms of the disease, which can severely limit daily functioning. There is much debate in the field regarding their measurement and classification and there are no FDA-approved treatments for negative symptoms despite an abundance of research. 3,4-Methylenedioxy methamphetamine (MDMA) is a schedule I substance that has emerged as a novel therapeutic given its ability to enhance social interactions, generate empathy, and induce a state of metaplasticity in the brain. This review provides a rationale for the use of MDMA in the treatment of negative symptoms by reviewing the literature on negative symptoms, their treatment, MDMA, and MDMA-assisted therapy. It reviews recent evidence that supports the safe and potentially effective use of MDMA to treat negative symptoms and concludes with considerations regarding safety and possible mechanisms of action.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

Objective: Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic- like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users. Methods: Six CHR cannabis users and six psychiatrically-healthy cannabis users comparable in intellectual, demographic, and cannabis use characteristics (including nontreatment-seeking status), participated in the study. Objective and subjective measures of cognition and cannabis reward, were completed before and after smoking half of an active (5.5% Δ9tetrahydrocannabinol [Δ9-THC]) or half of a placebo (0.0% Δ9-THC) cannabis cigarette, under randomized/double-blind conditions. Repeated measures ANOVA tested main effects of drug condition (active vs. placebo) and/or the drug condition × time (baseline vs. post-administration) interactions; groups were analyzed separately due to the small sample size. Results: CHR participants exhibited evidence of decreased objective response inhibition and aversive intoxication following active cannabis, relative to placebo. Psychomotor speed and cannabis-related attentional bias were also affected by cannabis intoxication. No such effects were observed in psychiatrically-healthy cannabis users. Conclusion: These findings provide further preliminary evidence of a deleterious cognitive and reward- related response to cannabis in individuals with preexisting risk for psychosis.

A pilot study of neurocognitive function in older and younger cocaine abusers and controls.

This pilot study compared basic neurocognitive functioning among older and younger cocaine abusers and control participants, as a preliminary assessment of whether specific cognitive deficits exist in an aged cocaine-abusing population. We hypothesized an interaction between aging and cocaine abuse, such that older cocaine abusers would exhibit decreased neuropsychological test performance relative to both younger cocaine abusers and older control participants. Four groups (n = 20 each) were examined: older cocaine abusers (ages 51-70), younger cocaine abusers (ages 21-39), and two non-illicit substance-using control groups. Basic neuropsychological and psychiatric measures were administered to all participants. Older participants performed more poorly than younger participants on the Mini-Mental State Examination (MMSE, p < .01), Digit Span Backward (p < .01), and Trail Making Test (TMT) Parts A and B (p < .01). Cocaine abusers performed more poorly than controls on TMT A (p < .01). Older and younger cocaine abusers used similar amounts of cocaine (p > .05). Older cocaine abusers performed more poorly than older control participants and younger cocaine abusers on the Digit Span Forward (p < .0125). Older cocaine abusers also performed more poorly than younger cocaine abusers on TMT A (p < .0125). This study provides preliminary evidence that older cocaine abusers use a significant amount of cocaine and that there is an interaction between aging and cocaine abuse on psychomotor speed, attention, and short-term memory. Future examination of neurocognitive function in older cocaine abusers is clearly warranted.

Specificity of verbal learning impairment and recovery in a marijuana-dependent male: the effects of sustained marijuana abstinence.

INTRODUCTION: We present the case of a young adult in treatment for marijuana dependence, with recurrent depression and a history of possible traumatic brain injury, complaining of concentration, memory, and initiation problems. METHODS: The patient was assessed longitudinally during treatment with a brief neuropsychological battery, as well as measures of marijuana use and mood. RESULTS: Testing at treatment baseline revealed performance that was generally in the high average range or higher on measures of reaction time and attention, with a selective impairment in verbal learning (borderline to extremely low range). Following 8 weeks of abstinence from marijuana, his verbal learning recovered to expected levels (high average range), with signs of improved learning strategy, efficiency, rate, and capacity. However, his reaction time and attention showed minimal evidence of change. CONCLUSIONS: This finding is consistent with the literature that demonstrates that marijuana-associated neurocognitive impairments may be most pronounced in the domain of verbal learning and may remit with abstinence. The clinical implications of these case findings and recommendations for neuropsychological assessment of marijuana abusers are discussed.

The acute and repeated effects of cigarette smoking and smoking-related cues on impulsivity.

INTRODUCTION AND AIMS: Impulsivity may be a risk factor that increases vulnerability to nicotine dependence. However, nicotine exposure itself may directly increase impulsivity. This is a secondary analysis of the first study in a controlled laboratory setting, which assessed the effects of nicotine administration (acute and repeated) and exposure to smoking cues on behavioural impulsivity in humans (ClinicalTrials.gov Identifier: NCT01395797). DESIGN AND METHODS: Twenty-seven smokers completed three tasks to assess behavioural impulsivity (the Immediate Memory Task and the Delayed Memory Task assessing response initiation, and the GoStop Task assessing response inhibition) following: (i) 4 days of cigarette smoking (nicotinised or denicotinised cigarette); (ii) acute cigarette smoking (nicotinised); and (iii) exposure to smoking-related cues. RESULTS: Four days of nicotinised cigarette smoking (vs. denicotinised) did not significantly increase Immediate Memory Task, Delayed Memory Task and GoStop scores. However, acute cigarette smoking increased GoStop impulsivity, but only following 4 days of smoking nicotinised cigarettes (P < 0.05). Exposure to smoking-related cues had no statistically significant effect on impulsivity. DISCUSSION AND CONCLUSIONS: Our results suggest that repeated nicotine exposure may sensitise subsequent acute nicotine effects on behavioural impulsivity in heavy smokers.

Correction: The Digital Marshmallow Test (DMT) Diagnostic and Monitoring Mobile Health App for Impulsive Behavior: Development and Validation Study.

[This corrects the article DOI: 10.2196/25018.].

The Digital Marshmallow Test (DMT) Diagnostic and Monitoring Mobile Health App for Impulsive Behavior: Development and Validation Study.

BACKGROUND: The classic Marshmallow Test, where children were offered a choice between one small but immediate reward (eg, one marshmallow) or a larger reward (eg, two marshmallows) if they waited for a period of time, instigated a wealth of research on the relationships among impulsive responding, self-regulation, and clinical and life outcomes. Impulsivity is a hallmark feature of self-regulation failures that lead to poor health decisions and outcomes, making understanding and treating impulsivity one of the most important constructs to tackle in building a culture of health. Despite a large literature base, impulsivity measurement remains difficult due to the multidimensional nature of the construct and limited methods of assessment in daily life. Mobile devices and the rise of mobile health (mHealth) have changed our ability to assess and intervene with individuals remotely, providing an avenue for ambulatory diagnostic testing and interventions. Longitudinal studies with mobile devices can further help to understand impulsive behaviors and variation in state impulsivity in daily life. OBJECTIVE: The aim of this study was to develop and validate an impulsivity mHealth diagnostics and monitoring app called Digital Marshmallow Test (DMT) using both the Apple and Android platforms for widespread dissemination to researchers, clinicians, and the general public. METHODS: The DMT app was developed using Apple's ResearchKit (iOS) and Android's ResearchStack open source frameworks for developing health research study apps. The DMT app consists of three main modules: self-report, ecological momentary assessment, and active behavioral and cognitive tasks. We conducted a study with a 21-day assessment period (N=116 participants) to validate the novel measures of the DMT app. RESULTS: We used a semantic differential scale to develop self-report trait and momentary state measures of impulsivity as part of the DMT app. We identified three state factors (inefficient, thrill seeking, and intentional) that correlated highly with established measures of impulsivity. We further leveraged momentary semantic differential questions to examine intraindividual variability, the effect of daily life, and the contextual effect of mood on state impulsivity and daily impulsive behaviors. Our results indicated validation of the self-report sematic differential and related results, and of the mobile behavioral tasks, including the Balloon Analogue Risk Task and Go-No-Go task, with relatively low validity of the mobile Delay Discounting task. We discuss the design implications of these results to mHealth research. CONCLUSIONS: This study demonstrates the potential for assessing different facets of trait and state impulsivity during everyday life and in clinical settings using the DMT mobile app. The DMT app can be further used to enhance our understanding of the individual facets that underlie impulsive behaviors, as well as providing a promising avenue for digital interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03006653; https://www.clinicaltrials.gov/ct2/show/NCT03006653.

An efficacy trial of adaptive interventions for alcohol use disorder.

BACKGROUND: Adaptive interventions, sometimes referred to as "stepped care", are those interventions in which the type or dosage of treatment offered to patients is tailored to baseline clinical presentation and then adjusted over time in response to patient progress or lack thereof. Currently, no adaptive brief interventions exist specifically for alcohol use disorder (AUD). METHOD: This study used a sequential multiple assignment randomized trial design with 160 individuals with AUD recruited both locally and nationally who had a goal to reduce or abstain from drinking. Participants received brief advice (BA) and then the study reassessed them three weeks later; the study randomized those who did not respond to BA, defined as reducing their drinking to low-risk guidelines, to two session of motivational interviewing (MI) or more BA. The study then reassessed participants at week 8. The study re-randomized nonresponders to receive either MI alone or MI plus behavioral self-control therapy (BSCT), also referred to as coping skills therapy, and evaluated participants at week 13. RESULTS: Overall, participants receiving any BSCT made the greatest reductions in drinking. Participants who received MI at week 4 and BSCT at week 8 outperformed all other groups. CONCLUSION: Findings reveal that prolonged treatment, more sessions, and/or a specific combination of MI and BSCT provided optimal outcomes. Future research should determine whether such an algorithm holds across heterogenous groups of individuals with AUD.