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Novel Addiction Treatment

Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
A Belin-Rauscent, J Lacoste, O Hermine, A Moussy, B J Everitt, David Belin
RATIONALE: Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties...
March 8, 2018: Psychopharmacology
Ritchy Hodebourg, Jennifer E Murray, Maxime Fouyssac, Mickaël Puaud, Barry J Everitt, David Belin
The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behavior. While cocaine reinforcement depends on the mesolimbic system, well established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis...
March 7, 2018: European Journal of Neuroscience
David N Greenfield
Internet and video game addiction has been a steadily developing consequence of modern living. Behavioral and process addictions and particularly Internet and video game addiction require specialized treatment protocols and techniques. Recent advances in addiction medicine have improved our understanding of the neurobiology of substance and behavioral addictions. Novel research has expanded the ways we understand and apply well-established addiction treatments as well as newer therapies specific to Internet and video game addiction...
April 2018: Child and Adolescent Psychiatric Clinics of North America
Nicole S Hernandez, Kelsey Y Ige, Elizabeth G Mietlicki-Baase, Gian Carlo Molina-Castro, Christopher A Turner, Matthew R Hayes, Heath D Schmidt
Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA)...
February 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
John Marsden, Camille Goetz, Tim Meynen, Luke Mitcheson, Garry Stillwell, Brian Eastwood, John Strang, Nick Grey
BACKGROUND: Cocaine use disorder (CUD) is a debilitating condition with no NICE-recommended medication or specific psychosocial interventions. In the United Kingdom (UK), general counselling (treatment-as-usual; TAU) is widely delivered, but has limited effectiveness. We tested the feasibility, safety and preliminary efficacy of a novel, adjunctive psychosocial intervention for CUD, called 'memory-focused cognitive therapy' (MFCT). METHODS: We did a two-arm, external pilot randomised controlled trial at a specialist community National Health Service addictions clinic in London, UK...
February 2, 2018: EBioMedicine
Deena M Walker, Eric J Nestler
Drug addiction involves long-term behavioral abnormalities that arise in response to repeated exposure to drugs of abuse in vulnerable individuals. It is a multifactorial syndrome involving a complex interplay between genes and the environment. Evidence suggests that the underlying mechanisms regulating these persistent behavioral abnormalities involve changes in gene expression throughout the brain's reward circuitry, in particular, in the mesolimbic dopamine system. In the past decade, investigations have begun to reveal potential genes involved in the risk for addiction through genomewide association studies...
2018: Handbook of Clinical Neurology
Terence Y Pang, Anthony J Hannan, Andrew J Lawrence
Relapse remains the most prominent hurdle to successful rehabilitation from alcoholism. The neural mechanisms underlying relapse are complex, but our understanding of the brain regions involved, the anatomical circuitry and the modulation of specific nuclei in the context of stress and cue-induced relapse have improved significantly in recent years. In particular, stress is now recognised as a significant trigger for relapse, adding to the well-established impact of chronic stress to escalate alcohol consumption...
February 22, 2018: Neuropharmacology
Yu Shi, Jiejing Li, Chunjiang Chen, Yongwu Xia, Yanxi Li, Pan Zhang, Ying Xu, Tingyu Li, Weihui Zhou, Weihong Song
Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8...
2018: Frontiers in Molecular Neuroscience
Jian-Feng Liu, Robert Seaman, Justin N Siemian, Rohan Bhimani, Bernard Johnson, Yanan Zhang, Qing Zhu, Marius C Hoener, Jinwoo Park, David M Dietz, Jun-Xu Li
Nicotine addiction and abuse remains a global health issue. To date, the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood. Trace amine-associated receptor 1 (TAAR1) is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictive-like behaviors. We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors. TAAR1 expression after nicotine treatment was evaluated by western blotting. c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release, respectively...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Brian J Sherman, Nathaniel L Baker, Lindsay M Squeglia, Aimee L McRae-Clark
BACKGROUND: More effective treatments for cannabis use disorder (CUD) are needed. Evidence suggests that biases in cognitive processing of drug-related stimuli are central to the development and maintenance of addiction. The current study examined the feasibility and effect of a novel intervention - approach bias modification (ApBM) - on cannabis approach bias and cue-reactivity. METHODS: A randomized, double-blind, sham-controlled proof-of-principle laboratory experiment investigated the effect of a four-session computerized ApBM training protocol on cannabis approach bias and cue-reactivity in non-treatment seeking adults age 18-65 with CUD (N = 33)...
April 2018: Journal of Substance Abuse Treatment
Michael Camilleri
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
R Christopher Pierce, Bruno Fant, Sarah E Swinford-Jackson, Elizabeth A Heller, Wade H Berrettini, Mathieu E Wimmer
Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development. For example, risk of cocaine addiction is highly heritable but genome-wide analyses comparing cocaine-dependent individuals to controls have not resulted in promising targets for drug development...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Yayi Swain, Peter Muelken, Mark G LeSage, Jonathan C Gewirtz, Andrew C Harris
Understanding factors contributing to individual differences in opioid addiction vulnerability is essential for developing more effective preventions and treatments. Sensation seeking has been implicated in addiction to several drugs of abuse, yet its relationship with individual differences in opioid addiction vulnerability has not been well established. The primary goal of this study was to evaluate the relationship between locomotor activity in a novel environment, a preclinical model of sensation-seeking, and individual differences in acquisition of i...
February 2, 2018: Pharmacology, Biochemistry, and Behavior
Matthew T Sutherland, Elliot A Stein
Drug abuse and addiction remain major public health issues, exemplified by the opioid epidemic currently devastating the United States. Treatment outcomes across substance use disorders remain unacceptably poor, wherein drug discovery/development for this multifaceted neuropsychiatric disorder focuses on single molecular-level targets. Rather, our opinion is that a systems-level neuroimaging perspective is crucial for identifying novel therapeutic targets, biomarkers to stratify patients, and individualized treatment strategies...
February 2018: Trends in Molecular Medicine
Erin M Miller, Jorge E Quintero, Francois Pomerleau, Peter Huettl, Greg A Gerhardt, Paul E A Glaser
Glutamate dysfunction has been implicated in a number of substance of abuse studies, including cocaine and methamphetamine. Moreover, in attention-deficit/hyperactivity disorder (ADHD), it has been discovered that when the initiation of stimulant treatment occurs during adolescence, there is an increased risk of developing a substance use disorder later in life. The spontaneously hypertensive rat (SHR) serves as a phenotype for ADHD and studies have found increased cocaine self-administration in adult SHRs when treated with the stimulant methylphenidate (MPH) during adolescence...
February 3, 2018: Neurochemical Research
Cesare Gridelli, Paul Baas, Fabrice Barlesi, Fortunato Ciardiello, Lucio Crinò, Enriqueta Felip, Shirish Gadgeel, Vali Papadimitrakopoulou, Luis Paz-Ares, David Planchard, Maurice Perol, Nasser Hanna, Assunta Sgambato, Francesca Casaluce, Filippo de Marinis
Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the past few years, new second-line therapies, beyond chemotherapy agents, have become available in clinical practice. To date, several options for the second-line treatment of non-oncogene-addicted NSCLC patients ranging from chemotherapy in combination with antivascular endothelial growth factor receptor to immunotherapeutics are available. In oncogene-driven tumors, the better knowledge of mechanisms of acquired resistance to earlier tyrosine kinase inhibitors is leading to novel active inhibitors now available/in development...
December 22, 2017: Clinical Lung Cancer
Andrew Quanbeck, David H Gustafson, Lisa A Marsch, Ming-Yuan Chih, Rachel Kornfield, Fiona McTavish, Roberta Johnson, Randall T Brown, Marie-Louise Mares, Dhavan V Shah
BACKGROUND: Despite the near ubiquity of mobile phones, little research has been conducted on the implementation of mobile health (mHealth) apps to treat patients in primary care. Although primary care clinicians routinely treat chronic conditions such as asthma and diabetes, they rarely treat addiction, a common chronic condition. Instead, addiction is most often treated in the US health care system, if it is treated at all, in a separate behavioral health system. mHealth could help integrate addiction treatment in primary care...
January 30, 2018: Journal of Medical Internet Research
James R McKay, David H Gustafson, Megan Ivey, Fiona McTavish, Klaren Pe-Romashko, Brenda Curtis, David A Oslin, Daniel Polsky, Andrew Quanbeck, Kevin G Lynch
BACKGROUND: New smartphone communication technology provides a novel way to provide personalized continuing care support following alcohol treatment. One such system is the Addiction version of the Comprehensive Health Enhancement Support System (A-CHESS), which provides a range of automated functions that support patients. A-CHESS improved drinking outcomes over standard continuing care when provided to patients leaving inpatient treatment. Effective continuing care can also be delivered via telephone calls with a counselor...
January 30, 2018: Trials
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