Refining the circuits of drug addiction: The ventral pallidum.

The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders.

Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

Brain Changes Linked to Cognitive Symptomatology in Homeless Youth.

Youth impacted by homelessness experience diminished cognition due to a variety of reasons including mental health symptoms, alcohol and substance use, and adverse childhood experiences. However, the status of specific brain regions which could impact important cognitive functions in homeless youth remains unclear. In this pilot comparative and correlational study, a series of demographic, psychological, cognitive assessments, and brain magnetic resonance imaging were performed in 10 male youth experiencing homelessness and 9 age-matched healthy male controls (age range: 18-25 years). Participants experiencing homelessness had significantly decreased regional brain gray matter tissue in comparison to the controls. Moreover, there were strong inverse correlations between the brain regions classically associated with executive decision-making (prefrontal cortices), depression (insular lobes), and conflict resolution (anterior cingulate), and the level of the symptoms detected by their questionnaires.

Rasgos de personalidad y síntomas psicopatológicos en adultos con trastornos por consumo de sustancias / Personality traits and psychopathological symptoms in adults with substance use disorders

This study aimed to characterize the personality traits of individuals withsubstance use disorders to verify the association and predictive value of personalitytraits for psychopathological symptoms and impulsivity. The participants were 77adults undergoing treatment at a psychosocial care center for alcohol and drug,who completed a sociodemographic and clinical data questionnaire, the NEO FiveFactor Inventory, the Adult Self-Report (ASR), and the Barratt Impulsiveness Scale(BIS-11). Most participants presented very low/low scores on extroversion andopenness factors. The five personality factors revealed significant associations withmost ASR subscales and BIS-11. High rates of neuroticism and low levels ofextraversion, agreeableness, and conscientiousness are related to a greateroccurrence of symptoms of anxiety, depression, attention, problems of thoughtand social isolation, somatic complaints, aggressive behavior, and impulsivity.According to the regression models, conscientiousness and neuroticism factorswere more significant for symptoms related to anxiety/depression, thoughtproblems, and rule-breaking behavior. (AU)

Este estudio buscó caracterizar los rasgos de personalidad de individuos con trastornos porconsumo de sustancias, medir la asociación y el valor predictivo de los rasgos de personalidadcon los síntomas psicopatológicos y la impulsividad. Participaron 77 adultos de un centro deatención psicosocial para el tratamiento de alcohol y drogas, quienes completaron uncuestionario de datos sociodemográficos y clínicos, el “Inventario de cinco factores NEO”, el“Autoinforme para adultos” (ASR) y la “Escala de impulsividad de Barratt” (BIS-11). Lamayoría de los participantes obtuvieron puntuaciones muy bajas/bajas en extraversión yapertura. Los cinco factores de personalidad revelaron asociaciones significativas con lamayoría de las subescalas del ASR y la BIS-11. Altos niveles de neuroticismo y bajos nivelesde extraversión, amabilidad y escrupulosidad se relacionan con una mayor ocurrencia desíntomas de ansiedad, depresión, atención, problemas de pensamiento y aislamiento social,quejas somáticas, comportamiento agresivo e impulsividad. Según los modelos de regresión,los factores de escrupulosidad y neuroticismo fueron más significativos para los síntomasrelacionados con la ansiedad/depresión, problemas de pensamiento y comportamiento deincumplimiento de reglas. (AU)

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using the ENIGMA consortium findings.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.

Substance Use Affects Type 1 Diabetes Pancreas Pathology: Implications for Future Studies.

Access to human pancreas samples from organ donors has greatly advanced our understanding of type 1 diabetes pathogenesis; however, previous studies have shown that donors have a high rate of substance use, and its impact on pancreatic histopathology in this disease is not well described. One-hundred-thirty-one type 1 diabetes and 111 control organ donor pancreata from persons 12-89 years of age (mean 29.8 ± 15.5 years) within the Network for Pancreatic Organ donors with Diabetes (nPOD) were examined for insulin positivity, insulitis, amyloid staining, acute and chronic pancreatitis, and chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis); findings were compared by history of substance use. A secondary analysis compared exocrine pancreatic histopathologic findings in type 1 diabetes versus control organ donors regardless of substance use history. We observed a high but congruent rate of substance use in type 1 diabetes and control organ donors (66.4% and 64% respectively). Among donors with type 1 diabetes (but not controls), islet amyloid (OR 9.96 [1.22, 81.29]) and acute pancreatitis (OR 3.2 [1.06, 9.63]) were more common in alcohol users while chronic exocrine changes (OR 8.86 [1.13, 69.31]) were more common in cocaine users. Substance use impacted the pancreata of donors with type 1 diabetes more than controls. Overall, despite similar rates of substance use, acute pancreatitis (15.3% versus 4.5%, p=0.0061), chronic pancreatitis (29.8% versus 9.9%, p=0.0001), and chronic exocrine changes (73.3% versus 36.9%, p<0.0001) were more common in type 1 diabetes donors than controls. Alcohol and/or cocaine use in type 1 diabetes organ donors increases exocrine pancreas pathology and islet amyloid deposition but does not affect insulitis or insulin positivity. Exocrine pathology in type 1 diabetes donors is common, and further study of the pathophysiology of these changes is needed.

Psychometric properties and longitudinal measurement invariance of the drug craving scale: Modification of the Polish version of the Penn Alcohol Craving Scale (PACS).

BACKGROUND: The Penn Alcohol Craving Scale (PACS) is an instrument with good psychometric properties that is widely used to assess alcohol craving. Based on the assumption that the experience of craving is independent of substance type, the Polish version of the PACS was modified to measure drug craving, thus creating the Penn Drug Craving Scale (PDCS). The analyses presented in the paper aim to verify the hypothesis that the PDCS has a unidimensional structure, is highly reliable and features longitudinal measurement invariance. METHODS: The research was conducted in 14 inpatient and 13 outpatient randomly selected facilities that provide psychosocial therapy to people with substance use disorder (SUD) in Poland, during June 2018 -July 2019. The data used for the analyses came from 282 patients diagnosed on the basis of ICD-10 criteria (F11.2-F19.2). The paper presents analyses with the application of: [1] confirmatory factor analysis (CFA) conducted on the basis of a polychoric correlation matrix and the WLSMV estimator; [2] a reliability estimate using Cronbach's alpha and coefficient omega; [3] verification of longitudinal measurement invariance between the beginning and end of therapy; [4] evaluation of criterion validity; [5] normalisation of the raw scores. RESULTS: The CFA results confirmed a unidimensional PDCS structure (RMSEA = 0.047, 95% CI: 0.000-0.103; CFI = 0.999; TLI = 0.999) and a high reliability of the scale (ω = 0.93). Moreover, a strict longitudinal measurement invariance of the instrument was confirmed. CONCLUSIONS: Accurate assessment of craving is possible only with valid and reliable instruments. Therefore, the psychometric properties of the PDCS were verified based on the latest statistical approaches. The scale is a valid and highly reliable tool featuring longitudinal measurement invariance and can be usefully used for research and clinical purposes. Thus, the Polish version of the PACS has been modified and successfully applied to the population of people with SUD.

Perfil epidemiológico dos usuários atendidos em centro de atenção psicossocial, álcool e drogas, em uma capital do nordeste brasileiro / Epidemiological profile of users served in Psychosocial Care Center, alcohol and drugs, in a capital of northeast Brazil / Perfil epidemiológico de usuarios servidos en Centro de Atención Psicosocial, alcohol y drogas, en uma capital del noreste de Brasil

Introdução:O uso de álcool e drogas é um problema crescente no Brasil e no mundo. Conhecer a epidemiologia dessa população nos serviços de atendimento aos usuários de substâncias psicoativas é um imperativo para melhor trata-los.Objetivo:descrever o perfil epidemiológico dos usuários de um Centro de Atenção Psicossocial Álcool e Drogas no Nordeste do Brasil. Metodologia:estudo descritivo, transversal, quantitativo. Por meio de planilha eletrônica, foram analisados os 281 prontuários de todas as pessoas maiores de 18 anos que utilizavam o serviço. Foi empregado o teste de qui-quadrado considerando o fator de p significativo menor ou igual a 0,05. O estudo foi aprovado eticamente.Resultados:homens, média de 42,06 anos, com nível fundamental de escolaridade e casados, formavam a maior parte da amostra. Foram estatisticamente relevantes: o maior consumo de álcool nos homens (p=0,03); maior escolaridade nos usuários de cocaína (p=0,013); maior tabagismo nos menos escolarizados (p=0,017); prole como proteção ao uso de cocaína (p=0,0006) e cannabis (p=0,0004); não ter filhos com menos uso de álcool (p=0,0015); uso precoce de cannabis (p=0,0002) e álcool (p=0,0065). Conclusões:perfis epidemiológicos em centros especializados podem nortear políticas públicas, na perspectiva de cuidado aos usuários de drogas (AU).

Introduction:The use of alcohol and drugs is a growing problem in Brazil and worldwide. Knowing the epidemiology of this population in services for users of psychoactive substances is an imperative to better treat them. Objective:to describe the epidemiological profile of users of a Psychosocial Care CenterAlcohol and Drugsin Northeastern Brazil. Methodology:descriptive, cross-sectional, quantitative study. Through an electronic spreadsheet, 281 medical records of people over 18 years of age who used the service were analyzed. The chi-square test was used considering the significant p factor less than or equal to 0.05. The study was ethically approved. Results:men, mean of 42.06 years, with basic education level and married, formed the majority of the sample. They were statistically relevant: the highest alcohol consumption in men (p = 0.03); higher education among cocaine users (p = 0.013); greater smoking in the less educated (p = 0.017); offspring as protection against the use of cocaine (p = 0.0006) and cannabis(p = 0.0004); not having children with less alcohol use (p = 0.0015); early use of cannabis (p = 0.0002) and alcohol (p = 0.0065). Conclusions:public policies expanding access to treatment for drug users are important solutions to this problem (AU).

Introducción: El uso de alcohol y drogas es un problema creciente en Brasil y en todo el mundo. Conocer la epidemiología de esta población en los servicios para usuarios de sustancias psicoactivas es un imperativo para tratarlos mejor.Objetivo: describir el perfil epidemiológico de los usuarios de un Centro de Atención PsicosocialAlcohol y Drogas en el noreste de Brasil.Metodología: estudio descriptivo, transversal, cuantitativo. Utilizando una hoja de cálculo electrónica, se analizaron los 281 registros de todas las personas mayores de 18 años que utilizaron el servicio. La prueba de chi-cuadrado se utilizó considerando el factor p significativo menor o igual a 0.05. El estudio fue aprobado éticamente.Resultados: hombres, promedio de 42.06 años, con nivel de educación básica y casados, formaron la mayoría de la muestra. Eran estadísticamente relevantes: el mayor consumo de alcohol en hombres (p = 0.03); educación superior entreusuarios de cocaína (p = 0.013); mayor tabaquismo en los menos educados (p = 0.017); descendencia como protección contra el uso de cocaína (p = 0,0006) y cannabis (p = 0,0004); no tener hijos con menos consumo de alcohol (p = 0.0015); uso temprano de cannabis (p = 0.0002) y alcohol (p = 0.0065).Conclusiones: los perfiles epidemiológicos en centros especializados pueden guiar las políticas públicas, desde la perspectiva de la atención a los consumidores de drogas (AU).

Real time monitoring of dopamine release evoked by mitragynine (Kratom): An insight through electrochemical sensor.

BACKGROUND: Mitragynine, the major indole alkaloid from Mitragyna speciosa has been reported previously to possess abuse liability. However, there are insufficient data suggesting the mechanism through which this pharmacological agent causes addiction. AIMS: In this study, we investigated the effects of mitragynine on dopamine (DA) level and dopamine transporter (DAT) expression from the rat's frontal cortex. METHODS: DA level was recorded in the brain samples of animals treated with acute or repeated exposure for 4 consecutive days with either vehicle or mitragynine (1 and 30 mg/kg) using electrochemical sensor. Animals were then decapitated and the brain regions were removed, snap-frozen in liquid nitrogen and immediately stored at -80 °C. DA level was quantified using Enzyme linked immunosorbent assay (ELISA) kits and DAT gene expression was determined using quantitative real time polymerase chain reaction (RT-qPCR). RESULTS/OUTCOME: Mitragynine (1 and 30 mg/kg) did not increase DA release following acute treatment, however, after repeated exposure at day 4, mitragynine significantly and dose dependently increased DA release in the frontal cortex. In this study, we also observed a significant increase in DAT mRNA expression at day 4 in group treated with mitragynine (30 mg/kg). CONCLUSION/INTERPRETATION: Data from this study indicates that mitragynine significantly increased DA release when administered repeatedly, increased in DAT mRNA expression with the highest tested dose (30 mg/kg). Therefore, the rewarding effects observed after mitragynine administration could be due to its ability to increase DA content in certain areas of the brain especially the frontal cortex.

Association patterns of cannabis abuse and dependence with risk of problematic non-substance-related dysregulated and addictive behaviors.

Co-occurrence of drug misuse with other dysregulated behaviors is common. This study was aimed at exploring the associations between the risk of presenting a clinically relevant condition involving non-substance-related addictive or dysregulated behaviors (as measured by the MultiCAGE CAD-4 screening), and cannabis abuse/dependence (CAST/SDS) scores, and the role of gender therein. Participants were recruited using stratified probabilistic sampling at the University of Granada. Mann-Whitney's U tests were used to compare male and female students in SDS and CAST scores. Associations between gender and MultiCAGE scores were estimated using the γ ordinal correlation index, and tested with χ2. For each MultiCAGE dimension, a Poisson-family mixed-effects model was built with either SDS or CAST as the main input variable, while controlling for nicotine and alcohol dependence, and relevant sociodemographic variables. Incidence rate ratios (IRR) were computed for SDS/CAST effects, and the significance threshold was family-wise Bonferroni-corrected. Gender differences were significant for cannabis dependence/abuse and all MultiCAGE scores for non-substance-related conditions, with males showing higher risk scores for excessive gambling, excessive internet use, excessive video gaming, and hypersexuality, and females presenting higher scores in dysregulated eating and compulsive buying. Cannabis dependence and abuse were significantly associated with a higher risk of problematic video gaming. These associations were mostly driven by males. Importantly, although risk of problematic video gaming was specifically associated with cannabis abuse/dependence, there was only a weak non-significant association between problematic video gaming and alcohol use scores. Risk of alcohol use problems, in turn, was strongly associated with all other non-substance-related problems (problematic gambling, excessive Internet use, dysregulated eating, compulsive buying, and hypersexuality). These differential associations can cast light on the etiological similarities and dissimilarities between problematic substance use and putative addictive behaviors not involving drugs.

Cannabinoids Drugs and Oral Health-From Recreational Side-Effects to Medicinal Purposes: A Systematic Review.

BACKGROUND: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. METHODS: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. RESULTS: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. CONCLUSIONS: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.

Childhood physical abuse and subsequent violent victimization among people who use illegal drugs in Vancouver, Canada.

BACKGROUND: Violent victimization is common among people who use illegal drugs (PWUD) and is a source of significant health-related harm. However, little attention has been paid to how antecedent childhood trauma among PWUD may contribute to the risk of victimization in adulthood. OBJECTIVE: This study sought to examine the relationship between childhood physical abuse and victimization by physical assault among adult PWUD. PARTICIPANTS AND SETTING: Data were derived from three prospective cohorts of PWUD in Vancouver, Canada between 2005 and 2018. METHODS: Childhood physical abuse was assessed using the Childhood Trauma Questionnaire. Generalized linear mixed modeling was used to estimate the relationship between childhood physical abuse and subsequent violent victimization, after adjustment for potential confounders. RESULTS: Among 2960 PWUD, including 1018 (34.39%) female participants, 1030 (34.8%) participants reported a history of moderate to severe childhood physical abuse, and 949 (32.06%) participants reported recent violent victimization at baseline. In a multivariate analysis, childhood physical abuse (Adjusted Odds Ratio [AOR] = 1.34, 95% confidence interval [CI]: 1.23-1.46) remained independently associated with violent victimization after adjustment for potential confounders. CONCLUSIONS: This study found a high prevalence of childhood physical abuse and that this was associated with a higher risk of subsequent violent victimization among PWUD in this setting. Greater support for PWUD with a history of childhood physical abuse is needed to decrease existing vulnerability to violence, including screening for and treatment of childhood trauma and related violence prevention.

Pharmacology of Drugs Used as Stimulants.

Psychostimulant, cardiovascular, and temperature actions of stimulants involve adrenergic (norepinephrine), dopaminergic (dopamine), and serotonergic (serotonin) pathways. Stimulants such as amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), or mephedrone can act on the neuronal membrane monoamine transporters NET, DAT, and SERT and/or the vesicular monoamine transporter 2 to inhibit reuptake of neurotransmitter or cause release by reverse transport. Stimulants may have additional effects involving pre- and postsynaptic/junctional receptors for norepinephrine, dopamine, and serotonin and other receptors. As a result, stimulants may have a wide range of possible actions. Agents with cocaine or MDMA-like actions can induce serious and potentially fatal adverse events via thermodysregulatory, cardiovascular, or other mechanisms. MDMA-like stimulants may cause hyperthermia that can be life threathening. Recreational users of stimulants should be aware of the dangers of hyperthermia in a rave/club environment.

Network centrality for the identification of biomarkers in respondent-driven sampling datasets.

Networks science techniques are frequently used to provide meaningful insights into the populations underlying medical and social data. This paper examines SATHCAP, a dataset related to HIV and drug use in three US cities. In particular, we use network measures such as betweenness centrality, closeness centrality, and eigenvector centrality to find central, important nodes in a network derived from SATHCAP data. We evaluate the attributes of these important nodes and create an exceptionality score based on the number of nodes that share a particular attribute. This score, along with the underlying network itself, is used to reveal insight into the attributes of groups that can be effectively targeted to slow the spread of disease. Our research confirms a known connection between homelessness and HIV, as well as drug abuse and HIV, and shows support for the theory that individuals without easy access to transportation are more likely to be central to the spread of HIV in urban, high risk populations.

Epigenetic Regulation of Circadian Clocks and Its Involvement in Drug Addiction.

Based on studies describing an increased prevalence of addictive behaviours in several rare sleep disorders and shift workers, a relationship between circadian rhythms and addiction has been hinted for more than a decade. Although circadian rhythm alterations and molecular mechanisms associated with neuropsychiatric conditions are an area of active investigation, success is limited so far, and further investigations are required. Thus, even though compelling evidence connects the circadian clock to addictive behaviour and vice-versa, yet the functional mechanism behind this interaction remains largely unknown. At the molecular level, multiple mechanisms have been proposed to link the circadian timing system to addiction. The molecular mechanism of the circadian clock consists of a transcriptional/translational feedback system, with several regulatory loops, that are also intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape shows profound changes in the addictive brain, with significant alterations in histone modification, DNA methylation, and small regulatory RNAs. The combination of these two observations raises the possibility that epigenetic regulation is a common plot linking the circadian clocks with addiction, though very little evidence has been reported to date. This review provides an elaborate overview of the circadian system and its involvement in addiction, and we hypothesise a possible connection at the epigenetic level that could further link them. Therefore, we think this review may further improve our understanding of the etiology or/and pathology of psychiatric disorders related to drug addiction.

Genetics of substance use disorders in the era of big data.

Substance use disorders (SUDs) are conditions in which the use of legal or illegal substances, such as nicotine, alcohol or opioids, results in clinical and functional impairment. SUDs and, more generally, substance use are genetically complex traits that are enormously costly on an individual and societal basis. The past few years have seen remarkable progress in our understanding of the genetics, and therefore the biology, of substance use and abuse. Various studies - including of well-defined phenotypes in deeply phenotyped samples, as well as broadly defined phenotypes in meta-analysis and biobank samples - have revealed multiple risk loci for these common traits. A key emerging insight from this work establishes a biological and genetic distinction between quantity and/or frequency measures of substance use (which may involve low levels of use without dependence), versus symptoms related to physical dependence.

Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis.

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). Voxel-based meta-analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta-analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.

Cutaneous foreign body microemboli-induced occlusive vasculopathy: A complication of illicit intravenous injection of oral opioid tablets.

Occlusive nonvasculitic vasculopathy is a process characterized clinically by retiform purpura and potential ulceration and necrosis of affected areas, secondary to blockage of small vessels without associated inflammatory vasculitis. Intravascular injection of foreign material is known to cause distal ischemia and necrosis due to thrombosis, local vasoconstriction, or microemboli formation. A 27-year-old male presented with retiform purpura and worsening distal fingertip necrosis of the right upper extremity accompanied by suspicious intravascular polarizable foreign material identified on skin, muscle, and vascular biopsies. We report a case that highlights concerning complications and dermatopathologic findings of intravascular injection of oral opioid tablets.

The effects of substance use on severe acute respiratory syndrome coronavirus infection risks and outcomes.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus (SARS-CoV2) infection rates are currently occurring at alarmingly accelerated rates. There is also a long-standing and concurrent rise in the prevalence and severity of substance use disorders (SUD). Therefore, the intersection between these two conditions needs to be carefully considered to ensure a more effective delivery of healthcare. RECENT FINDINGS: Generally, those with SUDs are more likely to have higher risk social determinants of health factors. Therefore, these patients are more likely to have barriers that can create difficulties in following appropriate infection control measures which in turn increases the risk of exposure to SARS-CoV2. In addition, these individuals have higher rates of medical comorbidities which increases the risk of all adverse outcomes, including mortality, from SARS-CoV2 infection. SUMMARY: Individuals with SUDs are at increased risk of both contracting SARS-CoV2 infection and suffering from worse outcomes afterwards. Though these risks of adverse outcomes are specific of SARS-CoV2 infection, the risk of exposure to other infectious diseases is increased in this population too. Healthcare providers and policymakers should then consider how to better protect this at-risk population and alleviate this increased disease burden.