Study Of Substance Use Disorders Research Articles

Assembly of an inexpensive rat jugular catheter button based on a split-septum needleless intravenous system

Rat intravenous self-administration is a widely-used animal model in the study of substance use disorders. Rats are tethered to a drug delivery system usually through a port or button that interfaces the drug delivery system with a chronic indwelling jugular vein catheter. These buttons can be purchased commercially but are costly, presenting a significant economic barrier for many researchers. Many researchers manufacture buttons in-house from a combination of individual custom made and commercially available components, resulting in large variation in terms of how the animals are handled and the longevity of catheter patency. We have developed a jugular catheter button that uses a split septum port to provide snap-on entry of a blunt cannula allowing for quick and easy attachment of the i.v. tubing. The port is constructed from commercially available split septum ports, surgical mesh and small metal cannula. The system is “needleless” which decreases the risk of infection and improves safety. The split-septum buttons are easily sterilized in-house adding to the reliability and decreases in the risk of infection. We have used this easily constructed, and inexpensive button for i.v. self-administration experiments in which 80 % of the rats maintained patency for a minimum of 35 days.•Inexpensive method to construct a self-administration backport button.•Utilizes inexpensive components already found in a research laboratory or commercially available.•Can be sterilized in-house without degrading glue or components.

A methodological checklist for fMRI drug cue reactivity studies: development and expert consensus.

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.

Is the relapse concept in studies of substance use disorders a 'one size fits all' concept? A systematic review of relapse operationalisations.

Relapse is a theoretical construct and empirical object of inquiry. It is unclear how relapse is operationalised with regard to the various phases in substance use disorders (SUD). The aim was to investigate relapse operationalisations in SUDs studies after short- and long-term abstinence and remission, recovery and slip/lapse. Systematic review using the following databases: Epistemonikos, Cochrane Central Register of Controlled Trials (CENTRAL and DARE), MEDLINE, EMBASE, Google Scholar, CINAHL, Web of Science and PsycINFO. Search returned 3426 articles, with 276 meeting the following inclusion criteria: empirical study published in English in a peer-reviewed journal; samples meet diagnostic criteria for dependence syndrome or moderate-severe drug use disorder or alcohol use disorder; reports relapse, abstinence, recovery, remission, slip or lapse. Review protocol registration: PROSPERO (CRD42020154062). Thirty-two percent of the studies had no definition of 'relapse'. Most relapse operationalisations were defined according to measure (26%), time (17%), use (26%) and amount and frequency (27%). Of the 16 studies with a follow-up duration of up to 2 years, one (6%) contained a definition of 'long-term abstinence'. Of the 64 studies with a follow-up duration of more than 2 years, four (6%) contained a definition of 'long-term abstinence'. Of those, one (2%) mentioned 'early relapse' and one (2%) mentioned 'late relapse'. Future research is needed to explore the possible difference between early and late relapse. Moreover, working to increase consensus on relapse operationalisations in SUD research is warranted. We identified no consensus on relapse operationalisations nor agreement on the differentiation between early and late relapse. The clinical utility of current relapse operationalisations seems low and may compromise knowledge accumulation about relapse and implementation of research into treatment.

Developmental Considerations for the Use of Naltrexone in Children and Adolescents.

Naltrexone (NTX) is a well-tolerated drug with a wide safety margin and mechanism of action that affords use across a wide variety of indications in adults and children. By antagonizing the opioid reward system, NTX can modulate behaviors that involve compulsivity or impulsivity, such as substance use, obesity, and eating disorders. Evidence regarding the disposition and efficacy of NTX is mainly derived from adult studies of substance use disorders and considerable variability exists. Developmental changes, plausible disease-specific alterations and genetic polymorphisms in NTX disposition, and pharmacodynamic pathways should be taken into consideration when optimizing the use of NTX in the pediatric population. This review highlights the current state of the evidence and gaps in knowledge regarding NTX to facilitate evidence-based pharmacotherapy of mental health conditions, for which few pharmacologic options exist.

Reconsidering research exclusion for serious mental illness: Ethical principles, current status, and recommendations

BackgroundHistorically, individuals managing serious mental illness (SMI) have often been excluded from research, typically because of concern that these individuals may not be able to understand and provide truly informed consent. As treatment has improved, the assumption that individuals managing SMI may not be capable of consent needs to be re-examined. Systematic exclusion from research may limit empirically tested treatments available for people managing SMI, and may contribute to the health care disparities seen in this population. ObjectivesThis article examines this issue by documenting current rates of research exclusion for high disease burden conditions, based on empirical review of studies in ClinicalTrials.gov. Research designCurrent rates of exclusion from studies for psychiatric conditions were assessed through systematic review of relevant clinical trials on ClinicalTrials.gov. SubjectsSubjects in this inquiry are either articles accessed in the literature reviews, or descriptions of studies in public data on ClinicalTrials.gov. MeasuresThe primary measure was a previously published coding system to document the extent and types of research exclusion related to psychiatric status. ResultsAmong studies of interventions for substance use disorders and chronic pain, individuals managing SMI were more likely to be excluded than those with other psychiatric disorders at statistically significant levels. This was not the case among studies of interventions for ischemic heart disease. In studies of substance use disorders, 9% explicitly excluded SMI and 83% could exclude people with SMI based on broader exclusion criteria. In studies of chronic pain these two categories of exclusion were 16% and 55%, and in studies of ischemic heart disease, these two categories of exclusion were 1% and 20%. ConclusionsEvidence indicates that it is ethically and scientifically more appropriate to exclude based on capacity to consent than membership in the group of individuals managing SMI. The discussion outlines techniques researchers can use for more equitable and generalizable sampling.

Dynamic Causal Modeling Self-Connectivity Findings in the Functional Magnetic Resonance Imaging Neuropsychiatric Literature.

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders.

Psychometric properties of the Anxiety Sensitivity Index-3 in adults with substance use disorders

Anxiety sensitivity, or the fear of anxiety-related sensations, has demonstrated relevance to a broad range of psychiatric conditions, including substance use disorders (SUDs). Anxiety sensitivity is typically measured through self-report instruments, most commonly the Anxiety Sensitivity Index-3 (ASI-3). Despite the widespread use of the ASI-3 in studies of SUDs, little is known about its psychometric properties within this population. Patients on an inpatient detoxification unit seeking treatment for SUDs (N = 1248) completed a battery of self-report measures, including the ASI-3. Psychometric properties of the ASI-3 were examined. An exploratory factor analysis with half of the sample (n = 624) supported a 3-factor structure corresponding to the ASI-3 subscales (Social Concerns, Cognitive Concerns, Physical Concerns). Confirmatory factor analysis was used to validate this 3-dimensional structure in a separate subsample (n = 624), resulting in adequate fit when testing a second-order hierarchical model. Internal consistency and convergent and discriminant validity results also supported the use of the ASI-3 in people with SUDs. Despite its widespread use in SUD research, this is the first psychometric investigation of the ASI-3 among individuals seeking treatment for SUDs.

Global sensitivity analysis of randomized trials with nonmonotone missing binary outcomes: Application to studies of substance use disorders.

In this paper, we present a method for conducting global sensitivity analysis of randomized trials in which binary outcomes are scheduled to be collected on participants at prespecified points in time after randomization and these outcomes may be missing in a nonmonotone fashion. We introduce a class of missing data assumptions, indexed by sensitivity parameters, which are anchored around the missing not at random assumption introduced by Robins (Statistics in Medicine, 1997). For each assumption in the class, we establish that the joint distribution of the outcomes is identifiable from the distribution of the observed data. Our estimation procedure uses the plug-in principle, where the distribution of the observed data is estimated using random forests. We establish asymptotic properties for our estimation procedure. We illustrate our methodology in the context of a randomized trial designed to evaluate a new approach to reducing substance use, assessed by testing urine samples twice weekly, among patients entering outpatient addiction treatment. We evaluate the finite sample properties of our method in a realistic simulation study. Our methods have been implemented in an R package entitled slabm.

Substance use disorders and COVID-19: the role of telehealth in treatment and research

ABSTRACT Telehealth, or the use of telecommunications and virtual technology to deliver health care and engage with patients outside of traditional health-care facilities, can play an important role in addressing the treatment and study of substance use disorders (SUDs) during the ongoing COVID-19 crisis. COVID-19 and related safety restrictions have thrust healthcare workers and researchers into a new reality of healthcare that relies heavily, or even exclusively, on telehealth methods. These changes have forced treatment providers and researchers to be agile in adopting these methods in order to maintain continuity of patient care and data collection. There are unique considerations that should be taken into account as telehealth practices continue to augment SUD care and research, even when restrictions have been lifted. Overall, we propose that telehealth can support innovation in treatment and research focused on SUDs and should be an integral part of our work, beyond COVID-19.

Impaired regulation of both addiction-related and primary rewards in individuals with internet gaming disorder

Poor executive function (EF) has been implicated in addictions. Among “hot” EFs (i.e., those involving motivations and emotions), poor regulation of craving has been proposed to underlie addiction development in substance-use disorders (SUDs), making such regulation a potential treatment target. However, regulation of craving remains poorly understood in internet gaming disorder (IGD). Additionally, prior studies of cold EFs (e.g., inhibition and cognitive flexibility under neutral conditions) in IGD have provided mixed results and mostly included only male subjects. We addressed these issues by instructing 54 participants (26 with IGD including males and females, and 28 control subjects) to perform a regulation-of-craving (ROC) task and a Stroop color-word-interference task. Compared to control subjects, individuals with IGD revealed deficits in regulation for both gaming- and food-related craving, but no differences in Stroop performance. The current study provides initial empirical support suggesting regulation impairments for both addiction-related and primary rewards among individuals with IGD. The findings are consistent with studies in SUDs, suggesting that impaired regulation of craving may be a relevant transdiagnostic construct across SUDs and behavioral addictions. The findings suggest targeting regulation of “hot” processes should be considered in IGD treatment development.

Genome-Wide Association Study of Opioid Cessation.

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

Drug-related Virtual Reality Cue Reactivity is Associated with Gamma Activity in Reward and Executive Control Circuit in Methamphetamine Use Disorders

Accumulated studies in substance use disorders indicated that the mesocorticolimbic reward circuit and executive control circuit played interactive roles in the cue-reactivity and gamma oscillatory in the cortex, as well as autonomic nervous activity was associated with it. This study aimed to explore the mechanism of processing drug-related cues. Sixty methamphetamine users were recruited and exposed to the drug-related virtual reality (VR) environments. Self-reported craving was assessed and skin conductance level (SCL) and heart rate variability were used to measure the autonomic nervous reactivity. With source estimation, gamma current density was used to measure the activity of medial prefrontal cortex/orbitofrontal cortex (MPFC/OFC) and dorsolateral prefrontal cortex (DLPFC) which are responsible for the mesocorticolimbic reward circuit and the executive control circuit. The VR drug-related cue induced an increased craving and SCL compared with the neutral condition. Gamma activity in MPFC/OFC and right DLPFC were decreased after cue exposure and predicted the SCL changes. However, no association was found between self-reported craving and electrophysiological response. Cue-reactivity in cortex and ANS, as well as their association, were observed in this study. Cue-induced electrophysiological responses were related to gamma activity in the mesocorticolimbic reward circuit and the executive control circuit.

VIGAN: Missing View Imputation with Generative Adversarial Networks.

In an era when big data are becoming the norm, there is less concern with the quantity but more with the quality and completeness of the data. In many disciplines, data are collected from heterogeneous sources, resulting in multi-view or multi-modal datasets. The missing data problem has been challenging to address in multi-view data analysis. Especially, when certain samples miss an entire view of data, it creates the missing view problem. Classic multiple imputations or matrix completion methods are hardly effective here when no information can be based on in the specific view to impute data for such samples. The commonly-used simple method of removing samples with a missing view can dramatically reduce sample size, thus diminishing the statistical power of a subsequent analysis. In this paper, we propose a novel approach for view imputation via generative adversarial networks (GANs), which we name by VIGAN. This approach first treats each view as a separate domain and identifies domain-to-domain mappings via a GAN using randomly-sampled data from each view, and then employs a multi-modal denoising autoencoder (DAE) to reconstruct the missing view from the GAN outputs based on paired data across the views. Then, by optimizing the GAN and DAE jointly, our model enables the knowledge integration for domain mappings and view correspondences to effectively recover the missing view. Empirical results on benchmark datasets validate the VIGAN approach by comparing against the state of the art. The evaluation of VIGAN in a genetic study of substance use disorders further proves the effectiveness and usability of this approach in life science.

Is Neural Processing of Negative Stimuli Altered in Addiction Independent of Drug Effects? Findings From Drug-Naïve Youth with Internet Gaming Disorder.

Difficulties in emotion regulation are commonly reported among individuals with alcohol and drug addictions and contribute to the acquisition and maintenance of addictive behaviors. Alterations in neural processing of negative affective stimuli have further been demonstrated among individuals with addictions. However, it is unclear whether these alterations are a general feature of addictions or are a result of prolonged exposure to drugs of abuse. To test the hypothesis of altered negative affect processing independent of drug effects, this study assessed neural function among drug-naïve youth with a behavioral addiction-Internet gaming disorder (IGD). Fifty-six young adults (28 with IGD, 28 matched controls) participated in fMRI scanning during performance of a well-validated emotion regulation task. Between-group differences in neural activity during task performance were assessed using a whole-brain, mixed-effects ANOVA with correction for multiple comparisons at currently recommended thresholds (voxel-level p<0.001, pFWE<0.05). Compared to controls, youth with IGD exhibited significantly blunted neural responses within distributed subcortical and cortical regions including the striatum, insula, lateral prefrontal cortex and anterior cingulate in response to negative affective cues, as well as during emotion regulation. Independent component analysis (ICA) further identified between-group differences in engagement of a fronto-cingulo-parietal network, involving decreased engagement in IGD youth relative to controls. Study findings are largely consistent with those from prior neuroimaging studies in substance-use disorders, thus raising the possibility that neural processing of negative affect may be blunted across drug and behavioral addictions independent of acute or chronic drug effects.

Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.

Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium.

The Utility of Magnetic Resonance Spectroscopy for Understanding Substance Use Disorders: A Systematic Review of the Literature.

The aim of this article is to present a systematic review of magnetic resonance spectroscopy (MRS) studies of substance use disorders. As a noninvasive and nonionizing imaging technique, MRS is being widely used in substance abuse research to evaluate the effects substances of abuse have on brain chemistry. Nearly 40 peer-reviewed research articles that focused on the utility of MRS in alcohol, methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, opiates, opioids, marijuana, and nicotine use disorders were reviewed. Findings indicate inconsistencies with respect to alterations in brain chemistry within each substance of abuse, and the most consistent finding across substances was decreased N-acetylaspartate and choline levels with chronic alcohol, methamphetamine, and nicotine use. Variation in the brain regions studied, imaging technique, as well as small sample sizes might explain the discrepancies in findings within each substance. Future well-designed MRS studies offer promise in examining novel treatment approaches in substance use disorders.

Ovarian hormones and drug abuse.

There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women's health. In this review we will discuss findings from clinical and preclinical studies of (1) reproductive cycle phase; (2) endogenous ovarian hormones; and (3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.

Economic analysis of substance use disorders

Economic studies of substance use disorders comprise a growing and important specialization within the broad and interdisciplinary field of addiction research. The proposed symposium highlights methods and findings from recent economic investigations describing social and economic consequences of substance use and dependence. Kathryn McCollister's paper describes the cost-effectiveness of recovery management checkups in promoting abstinence and reducing the number of substance use related problems.

Addictive Disorders: Finding the Predisposing Traits

Addictive Disorders: Finding the Predisposing Traits

Evaluating Dependence Criteria for Caffeine.

Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year (n=167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful.