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Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects. Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history. Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history. Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.
Copyright © 2018. Published by Elsevier B.V.
Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.
© The Author(s) 2016.
Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.
Copyright ©ERS 2015.
Brief interventions aimed at reducing alcohol use among youth may interrupt a possible developmental progression to more serious substance use if they can also affect the use of other illicit drugs. This meta-analysis examined the findings of recent research on the effects of brief alcohol interventions for adolescents and young adults on both alcohol and illicit drug use. Eligible studies were those using randomized or controlled quasi-experimental designs to examine the effects of brief alcohol interventions on illicit drug use outcomes among youth. A comprehensive literature search identified 30 eligible study samples that, on average, included participants age 17, with 57 % male participants and 56 % White youth. Three-level random-effects meta-analyses were used to estimate mean effect sizes and explore variability in effects. Overall, brief interventions targeting both alcohol and other drugs were effective in reducing both of these substances. However, the brief interventions that targeted only alcohol had no significant secondary effects on untargeted illicit drug use. The evidence from current research, therefore, shows modest beneficial effects on outcomes that are targeted by brief interventions for youth, but does not show that those effects generalize to untargeted illicit drug use outcomes.
BACKGROUND - There have been inconsistent findings on the association between current drug use and HIV disease progression and virologic suppression. Drug use was often measured using self-report of historical use. Objective measurement of current drug use is preferred.
METHODS - In this cross-sectional study, we assessed drug use through Computer-Assisted Self Interviews (CASI) and point-of-care urine drug screen (UDS) among 225 HIV-infected patients, and evaluated the association between current drug use and virologic suppression.
RESULTS - About half (54%) of participants had a positive UDS, with a lower self-reported rate by CASI (42%) (Kappa score = 0.59). By UDS, 36.0% were positive for marijuana, 25.8% for cocaine, 7.6% for opiates, and 2.2% for methamphetamine or amphetamine. Factors associated with virologic suppression (plasma HIV RNA <50 copies/mL) were Caucasian race (P = 0.03), higher CD4 count (P < 0.01), current use of antiretroviral therapy (ART) (P < 0.01), and a negative UDS (P < 0.01). Among 178 current ART users, a positive UDS remained significantly associated with lower likelihood of virologic suppression (P = 0.04).
CONCLUSIONS - UDS had good agreement with CASI in detecting frequently used drugs such as marijuana and cocaine. UDS at routine clinic visits may provide "real-time" prognostic information to optimize management.
Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.
Drug addiction is a chronic and complex brain disease, adding much burden on the community. Though numerous efforts have been made to identify the effective treatment, it is necessary to find more novel therapeutics for this complex disease. As network pharmacology has become a promising approach for drug repurposing, we proposed to apply the approach to drug addiction, which might provide new clues for the development of effective addiction treatment drugs. We first extracted 44 addictive drugs from the NIDA and their targets from DrugBank. Then, we constructed two networks: an addictive drug-target network and an expanded addictive drug-target network by adding other drugs that have at least one common target with these addictive drugs. By performing network analyses, we found that those addictive drugs with similar actions tended to cluster together. Additionally, we predicted 94 nonaddictive drugs with potential pharmacological functions to the addictive drugs. By examining the PubMed data, 51 drugs significantly cooccurred with addictive keywords than expected. Thus, the network analyses provide a list of candidate drugs for further investigation of their potential in addiction treatment or risk.
Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive-behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest-state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, and dorsal putamen) in a sample of 40 adult male prison inmates (n = 22 diagnosed with SUD; n = 18 without SUD). Relative to the non-SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive-behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive-behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive-behavioral control.
Copyright © 2014 Wiley Periodicals, Inc.
Many psychostimulants, including cocaine and methamphetamine, interact with sigma (σ) receptors at physiologically relevant concentrations. The potential therapeutic relevance of this interaction is underscored by the ability to selectively target σ receptors to mitigate many behavioral and physiological effects of psychostimulants in animal and cell-based model systems. This chapter begins with an overview of these enigmatic proteins. Provocative preclinical data showing that σ ligands modulate an array of cocaine and methamphetamine effects are summarized, along with emerging areas of research. Together, the literature suggests targeting of σ receptors as an innovative option for combating undesired actions of psychostimulants through both neuronal and glial mechanisms.
© 2014 Elsevier Inc. All rights reserved.