Advances in drug and alcohol research最新文献

Introduction: Cannabis use is linked to the risk of developing a Cannabis Use Disorder (CUD), which can often be chronic. Early identification of problematic cannabis use is crucial to lower the risk of CUD and associated adverse effects. However, the factor structure of the widely used Cannabis Use Disorder Identification Test (CUDIT) remains ambiguous. Furthermore, the impact of age and gender on CUD assessed with CUDIT is unknown. Exploring cannabis use motives has been proposed to better understand susceptibility to CUD. This study aims to clarify the CUDIT's factor structure, its links to cannabis use motives, and the influence of age and gender on CUD.

Materials and methods: We analyzed data from 3454 people who use cannabis (20.5% women; mean age = 30.31 years), collected from a Swiss online survey. Participants were categorized into four groups: younger men, younger women, older men, older women. Principal Component Analysis and Confirmatory Factor Analysis tested the factor structure of the revised CUDIT version (CUDIT-R). Structural Equation Modeling explored whether the influence of use motives on the CUDIT-R factors differs between demographic groups.

Results: The results suggest that the CUDIT-R scale is best represented by two factors: Use Intensity (Cronbach's $\alpha$ = 0.71) and Awareness of Problematic Use (Cronbach's $\alpha$ = 0.72). Use Intensity was lowest for younger women, and younger participants were more aware of negative effects. Gender, age, and use motives uniquely relate with both CUDIT-R factors, highlighting the CUDIT-R's potential to guide early identification and treatment of individuals at risk for CUD.

Background: Alcohol-related brain damage caused by heavy alcohol misuse is associated with cognitive-motor impairment and white matter (WM) degeneration. Oligodendrocytes and myelin are major targets, but the underlying mechanisms remain incompletely characterized, particularly in humans.

Purpose: This study investigates the nature of oligodendrocyte dysfunction in anterior frontal lobe tissue from humans with alcohol use disorder (AUD), focusing on molecular and biochemical pathologies that may underlie WM ARBD.

Methods: Cores of fresh frozen human postmortem frontal lobe WM from adults with AUD or no history of substance use disorder (N = 6/group) were analyzed with duplex enzyme-linked immunosorbent assays, multiplex immunoassays, and multiplex RNA hybridization panels.

Results: AUD anterior frontal lobe WM tissue exhibited myelin loss with significant changes in oligodendrocyte/myelin glycoprotein immunoreactivity and mRNA expression, increased glial fibrillary acidic protein, and reduced expression of mRNA transcripts encoding upstream components of the insulin and insulin-like growth factor networks, aspartyl-asparaginyl-β-hydroxylase, and the Notch signaling pathway. In contrast, neuroinflammatory mediators and Alzheimer's disease (AD) biomarkers were largely unaffected.

Conclusion: Human AUD anterior frontal lobe WM pathology is accompanied by significant alterations in oligodendrocyte and astrocyte function, with alterations in Notch and insulin/IGF signaling. The findings provide new information on the mechanisms of AUD-mediated WM degeneration as well as potential strategies for diagnosing ARBD in humans.

The impact of compulsive behaviors (aka addictions), whether substance- or behavioral-based, is substantial. The acronym HALT (Hungry, Angry, Lonely, Tired) has long been used in recovery. This paper provides a discussion of the history and basic concept, with application for relapse prevention and increasing resilience for mental health. It further offers a rationale for expanding this skill set with new and easily applied contextual domains. Using a familiar tool as a building block provides a framework for helping individuals with current or past compulsive behaviors, and for those assisting them. This may decrease relapse incidents which impact the individual and society.

Background: Adolescents with externalizing (EXT) disorders, such as attention-deficit/hyperactivity disorder and conduct disorder-characterized by impulsivity and rule-breaking, are at elevated risk for substance use disorders (SUDs), partly due to deficits in risky decision-making. Sex differences in this association are understudied. Neuroimaging research shows females and males with EXT disorders exhibit different brain activation patterns during risky decisions. This study will explore how these sex differences relate to the development of problematic substance use in youth with EXT disorders.

Method: A total of 115 (78 males, 37 females) drug-naive adolescents with EXT psychopathology performed the Balloon Analogue Risk Task (BART) during magnetic resonance imaging to assess risky decision-making brain activation. Then, participants and their guardians completed questionnaires at 6-month intervals to assess problematic substance use. Statistical analyses evaluated sex differences in brain activation-both parametrically modulated and unmodulated-within a priori-selected regions associated with risky decision-making and problematic substance use, using Cox proportional hazards models.

Results: Higher modulated brain activation (as explosion probability increased) during the choice phase contrast, Choose Inflate-Choose Win, was associated with a lower hazard of problematic substance use in the right nucleus accumbens (Hazard Ratio (HR) = 0.68, 95% CI [0.49, 0.94], p = 0.01). This association was significant for females, but not for males, with the hazard ratios being significantly different between sexes. In the right nucleus accumbens, higher unmodulated choice phase activation in males was associated with lower hazard of problematic substance use (HR = 0.60, 95% CI [0.37, 0.97], p = 0.03); and in the right subgenual anterior cingulate cortex, higher unmodulated activation in this same contrast in females was associated with a lower hazard of problematic substance use [HR = 0.49, 95% CI (0.24, 0.97), p = 0.03].

Conclusion: This study offers insight into sex differences in risky decision-making neural mechanisms and SUD risk among youth with EXT disorders. Our findings suggest typical risk signaling in the reward-processing network (nucleus accumbens and subgenual anterior cingulate cortex) may protect against substance use, particularly in females with EXT disorders. These findings emphasize the need for further sex-specific research and interventions for youth with EXT disorders.

Background: Alcohol use disorder (AUD) marked by heavy chronic or binge alcohol consumption, causes cerebellar and white matter (WM) atrophy with cognitive-motor impairments. Major pathological features of alcohol-related brain damage (ARBD) include alterations in WM integrity with myelin loss, and cerebellar degeneration with neuronal loss.

Purpose: This study characterizes molecular and biochemical oligodendrocyte-related pathology in cerebellar tissue from donors with AUD to better understand the mechanisms of ARBD in humans.

Methods: Cores of cerebellar vermis, including cortex and underlying WM from adult human postmortem AUD and control brains, were processed for RNA and protein analyses using duplex and multiplex panels.

Results: AUD cerebellar WM had significant alterations in immature and mature oligodendrocyte protein and mRNA expression, and reduced expression of hepatocyte growth factor, Akt and GSK-3β signaling molecules, and Notch pathway activation. Moreover, the only significant AUD-related alteration in cerebellar cytokine/chemokine expression was reduced IL-16 immunoreactivity.

Conclusion: Human AUD WM degeneration is associated with oligodendrocyte dysfunction, which mechanistically could be mediated by impairments in insulin/IGF signaling through Akt/GSK-3β or Notch pathway activation. Future studies should focus on the non-invasive detection and monitoring of AUD-related oligodendrocyte pathology through the analysis of cell-type-specific exosomes isolated from peripheral blood.

During pregnancy, the fetal brain undergoes rapid development and is highly sensitive to environmental influences. Understanding the intricate processes that underlie fetal brain development will be critical for advancing maternal-fetal health and mitigating the risks associated with developmental brain disorders. Nonhuman primate (NHP) animal models provide a unique and highly translational platform for studying brain development during pregnancy due to the close anatomical, physiological, and behavioral resemblance of these animals to humans. Our review explores the use of NHP models in elucidating key milestones of prenatal brain maturation and the mechanisms that govern typical and atypical development. We further examine the impact of environmental insults on fetal brain development, including air pollution, infection, ionizing radiation, and exposure to toxicants, and highlight the ways in which these factors can disrupt brain development and neural circuitry, leading to long-term cognitive and behavioral deficits. Recent studies demonstrate that the baboon (Papio hamadryas) animal model provides a fruitful yet underused translational model for research related to environmental adverse effects on pregnancy. Lastly, we review the effects of drugs of abuse on the developing fetal brain, highlighting the underlying biological mechanisms identified through clinical and laboratory studies. A combined approach offers a comprehensive understanding of the vulnerabilities of the developing nervous system, informing new strategies for the treatment and prevention of neurodevelopmental disorders.

Alcohol withdrawal is characterized by various symptoms that include pain and negative affect in the absence of the drug. The neural underpinnings of these behaviors are not entirely understood, but orexin has emerged as a candidate target for the treatment of substance use disorders. Here, we explored changes in orexin system-related gene expression in brain regions important for mediating reward and stress, including the ventral tegmental area (VTA) and extended amygdala (including the central amygdala, nucleus accumbens shell, and bed nucleus of the stria terminalis), in adolescent and adult female Wistar rats following chronic alcohol exposure. We observed higher numbers of Hcrtr1- (orexin receptor 1)-expressing neurons in the VTA of adolescent and adult female rats during withdrawal from chronic alcohol exposure. The number of Hcrt1+ VTA neurons was negatively correlated with thermal sensitivity in adolescent female rats and anxiety-like behavior in adult female rats. These data suggest that chronic alcohol effects on orexin receptor expression in the VTA are related to specific behaviors that manifest during withdrawal, highlighting potential avenues for targeting alcohol withdrawal-associated behaviors across development.

At-risk alcohol and illicit drug use are risk factors for disease and in-hospital complications. This study investigated whether clinicians document substance use in the electronic records of acutely hospitalized internal medicine patients. Alcohol and illicit drug positive patients were identified using prospectively gathered substance use data from a study sample comprising 2,872 patients included from November 2016 to December 2017 at an internal medicine hospital in Oslo, Norway. These data were unknown to hospital staff. Whether physicians recorded quantitative substance use assessments and interventions was examined in patients with study-verified alcohol use in excess of low-risk guidelines (Alcohol Use Disorder Identification Test-4 scores [AUDIT-4] of ≥5 for women and ≥7 for men) and/or illicit drug use (one or more illicit drug detected by liquid chromatography-mass spectrometry [LC-MS] analysis). Among 548 study-verified alcohol-positive patients, physicians documented quantity and frequency (QF) of use in 43.2% (n = 237) and interventions in 22.0% (n = 121). Alcohol interventions were associated with harmful drinking (AUDIT-4 ≥9 points; adjusted odds ratio [AOR] = 4.87; 95% CI: 2.54-9.31; p < 0.001) and QF assessments (AOR = 3.66; 95% CI: 1.13-11.84; p = 0.02). Among 157 illicit-positive patients, drug use was described quantitatively in 34.4% (n = 54) and interventions in 26.0% (n = 40). The rate of quantitative alcohol and illicit drug use assessment by hospital physicians is poor, with a correspondingly low intervention rate. Important opportunities for attenuating or intervening in at-risk alcohol and illicit drug use are missed.

As part of a broader qualitative study aimed at understanding the experiences and opinions of adolescents and young adults (AYA) who do not drink alcohol in Switzerland, participants were questioned about their perceptions of the term "abstinence" in the context of alcohol non-consumption. Twelve focus groups were conducted with 63 participants (36 females, 27 males), aged between 14 years and 20 years. Participants were grouped by gender, age (based on Swiss alcohol laws), and drinking status (non-drinker or drinker). The discussions were recorded and transcribed, and thematic content analysis was used to identify and categorize key themes. The terms "abstinence," "abstainer," and "abstention" were generally considered unsuitable when describing young people who do not consume alcohol regardless of the drinking status of the participants. The connotation carried by the terms was mostly perceived as religious, sexual, negative and stigmatizing. "Abstinence" was considered more appropriate for adults who have stopped drinking due to alcohol-related issues. When referring to youths, terms such as "non-drinking," "non-drinkers" or "alcohol non-consumption" were preferred, especially to better integrate non-drinking youths and positively highlight their choices in preventive and educational initiatives.