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IMPORTANCE: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. OBJECTIVE: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. EVIDENCE REVIEW: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. FINDINGS: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

BackgroundChronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment.MethodsA multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms.ConclusionThis study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD.Trial registrationClinicalTrials.gov Identifier: NCT04648228.

Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems., A spectrum of problematic alcohol use Alcohol is one of the most commonly used psychoactive substances worldwide. Its use remains controlled in a majority of people but is also a [...]

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

Objective: Many college women report engaging in weight control strategies, yet little is known about which strategies are used and how often. The current study's goal was to evaluate the factor structure of a comprehensive list of weight control behaviors used in the previous 24-hours. Participants: Undergraduate women (N = 286) were recruited from a southwestern university. Methods: Participants reported their weight control strategies for the previous 24 hours on a checklist compiled from previous studies. Results: Exploratory and confirmatory factor analyses indicated that a 14-item, 2-factor ("Consumption-reduction", "Health-focused" Strategies) structure was a good fit of the data. Tests of longitudinal measurement invariance found support for using the checklist to make meaningful comparisons across time. Conclusions: This study developed a checklist of past 24-hour weight-control strategy usage, thereby providing a step toward developing an instrument that may be used for weight control or early intervention for disordered eating.

Alcohol use is highly comorbid with depression, especially among college students, whose rates of both phenomena are higher than in the general population. The self-medication hypothesis (i.e., alcohol use is negatively reinforced via the alleviation of negative affect) has dominated explanatory models of comorbidity. However, self-regulation has also demonstrated cross-sectional relationships with both depression and alcohol problems and may contribute to the development of alternative comorbidity models. Self-regulation introduces three alternative models that can be tested empirically: (a) a depressed regulation model, (b) a central nervous system depressant model, and (c) a self-regulatory failure model. The purpose of this study was to test the utility of these models (in addition to the self-medication hypothesis) by examining the temporal precedence in the relations between self-regulation, depressive symptoms, and alcohol problems among heavy-drinking college students (N = 393) over 5 assessment points (baseline, 1 month, 6 months, 12 months, and 16 months) using an autoregressive cross-lagged model. Lower self-regulation, and higher alcohol problems and depressive symptoms, prospectively predicted higher depressive symptoms. Higher alcohol problems and lower self-regulation prospectively predicted higher alcohol problems. Only self-regulation prospectively predicted self-regulation. These results were consistent across multiple time points. Findings are consistent with a self-regulatory failure model of depressive symptoms and alcohol problems. Therefore, self-regulation may be an important etiological variable and potential intervention target to reduce both alcohol problems and depressive symptoms among college students. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

ObjectiveBehavioral economic theory suggests that a reduction in alcohol use is most likely when there is an increase in rewarding substance-free activities. Anxiety has also been linked to heavy drinking, and strategies to reduce anxiety may enhance alcohol interventions. The goal of this 2-site randomized controlled clinical trial was to evaluate the efficacy of a brief alcohol intervention that was supplemented with either a behavioral economic substance-free activity session (SFAS) or a relaxation training (Relaxation training [RT]) session.MethodParticipants were 393 college students (61% female, mean age = 18.77 years) who reported 2 or more past-month heavy drinking episodes. Participants were randomized to 1 of 3 conditions: (a) assessment; (b) alcohol brief motivational intervention (BMI) plus SFAS; or (c) BMI plus RT. Both treatment conditions included 2 in-person sessions plus a phone booster session. Outcomes were evaluated 1-, 6-, 12-, and 16-months postintervention.ResultsGeneralized linear mixed models indicated that the combination of a BMI plus either the SFAS or RT was associated with significant reductions in alcohol use and problems across the 16-month follow-up compared with assessment only. There were no significant differences between the two active treatment conditions. Changes in proportional reinforcement from substance-related activities, and protective behavioral strategies mediated treatment effects.ConclusionTwo-session (plus booster) interventions that combine BMI and either substance-free activity enhancement or RT can result in enduring reductions in alcohol misuse among college drinkers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: The US Department of Veterans Affairs, Department of Defense (VA/DoD) clinical guidelines recommend extended-release naltrexone (XR-NTX) as a treatment option for moderate-to-severe alcohol use disorder (AUD); however, contemporary real-world outcomes related to this guideline are lacking. This retrospective, observational, descriptive study examined treatment patterns and healthcare resource use (HCRU) among veterans with an AUD diagnosis who initiated XR-NTX. Methods: Veterans with incident AUD who initiated XR-NTX between 8/2014 and 11/2018 were identified. Treatment patterns and HCRU were assessed during the 1-year baseline period before and following XR-NTX initiation (the index date). Results: Of the 3665 VA patients (mean [SD] age: 46 [12.5] years; male: 89.7%; White: 76.9%) included in the study, time from AUD diagnosis to XR-NTX initiation was highly variable (mean [range]: 13.6 [0-50.5 months]). Patients received a mean [SD] of 6.8 [6.1] XR-NTX administrations; 44.4% received ⩾6. Mean [SD] time to XR-NTX discontinuation was 93.4 [75.7] days, and 31.3% of discontinuing patients resumed XR-NTX therapy. Of those who received other subsequent medications for AUD, 38.6% (acamprosate) to 47.8% (disulfiram) re-initiated XR-NTX. The proportion of patients with ⩾1 inpatient admissions decreased during follow-up compared with baseline (all-cause: 61.5% to 37.8%; AUD-related: 58.0%-35.4%); with a smaller decrease observed in emergency department (ED) visits. In contrast, more patients had ⩾1 outpatient visits during follow-up (all-cause: 97.5%-99.7%; AUD-related: 84.4%-92.7%). Compared with baseline, mean number of inpatient admissions and ED visits decreased during follow-up, while the number of outpatient visits increased for both all-cause and AUD-related care. Conclusions: Among VA patients with AUD who initiated XR-NTX, we observed reductions in all-cause and AUD-related acute care, and increases in outpatient care. This finding demonstrates a possible transition from acute, inpatient treatment to long-term, outpatient care that may reflect a reduction in disease severity. Additional research is warranted. [ABSTRACT FROM AUTHOR]

Objective: The Alcohol Addiction Research Domain Criteria (AARDoC) is an organizational framework for assessing heterogeneity in addictive disorders organized across the addiction cycle domains of incentive salience, negative emotionality, and executive functioning and may have benefits for precision medicine. Recent work found pretreatment self-report items mapped onto the addiction cycle domains and predicted 1- and 3-year alcohol use disorder treatment outcomes. Given the potential utility of the addiction cycle domains for predicting relevant treatment outcomes, this study sought to evaluate the longitudinal measurement invariance of the domains. Method: We conducted a secondary analysis of individuals with alcohol use disorder (n = 1,383, 30.9% female, 76.8% non-Hispanic White, 11.2% Hispanic) who participated in the COMBINE study. Eleven items assessed at pre- and posttreatment were included in exploratory structural equation modeling (ESEM) and longitudinal invariance analyses. Results: The pre- and posttreatment ESEM models had factor loadings consistent with the three addiction cycle domains and fit the data well. The ESEM factor structure was invariant from pre- to posttreatment (representing configural invariance) and metric invariance (factor loadings) was largely supported, but analyses failed to support scalar invariance (item-level thresholds) of the addiction cycle domains. Conclusions: A three-factor structure representing addiction cycle domains can be modeled using brief self-report measures pre- and posttreatment. Individuals demonstrated a downward shift in the level of item endorsement, indicating improvement with treatment. Although this 11-item measure might be useful at baseline for informing treatment decisions, results indicate the need to exercise caution in comparing the addiction cycle domains pre- to posttreatment within persons. Public Health Significance Statement: The addiction cycle domains of reward/incentive salience, relief/negative emotionality, and executive functioning, which are based on a neurobiological model of alcohol use disorder, may have clinical utility in predicting alcohol use disorder treatment response and recovery outcomes, but more work is needed before domain scores can be used to assess changes within individuals across time. [ABSTRACT FROM AUTHOR]