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David Nutt

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https://www.readbyqxmd.com/read/28247526/naltrexone-ameliorates-functional-network-abnormalities-in-alcohol-dependent-individuals
#1
Laurel S Morris, Kwangyeol Baek, Roger Tait, Rebecca Elliott, Karen D Ersche, Remy Flechais, John McGonigle, Anna Murphy, Liam J Nestor, Csaba Orban, Filippo Passetti, Louise M Paterson, Ilan Rabiner, Laurence Reed, Dana Smith, John Suckling, Eleanor M Taylor, Edward T Bullmore, Anne R Lingford-Hughes, Bill Deakin, David J Nutt, Barbara J Sahakian, Trevor W Robbins, Valerie Voon
Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects...
February 28, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28224686/addiction-research-and-theory-a-commentary-on-the-surgeon-general-s-report-on-alcohol-drugs-and-health
#2
Aldo Badiani, Kent C Berridge, Markus Heilig, David J Nutt, Terry E Robinson
The Office of the Surgeon General recently produced its first Report on the consequences of alcohol and drug abuse on health, making several very laudable policy recommendations. The Report also emphasizes the importance of adequate funding for biomedical research, which is good news for both researchers and patients. However, the Report is marred by a biased viewpoint on the psychology and neurobiology of drug addiction. We highlight here four controversial issues that were depicted as facts in the Report, thereby potentially misleading non-expert readers about the current state-of-the-art understanding of the psychology and neurobiology of drug addiction...
February 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28216062/nalmefene-reduces-reward-anticipation-in-alcohol-dependence-an-experimental-functional-magnetic-resonance-imaging-study
#3
Darren R Quelch, Inge Mick, John McGonigle, Anna C Ramos, Remy S A Flechais, Mark Bolstridge, Eugenii Rabiner, Matthew B Wall, Rexford D Newbould, Björn Steiniger-Brach, Franz van den Berg, Malcolm Boyce, Dorrit Østergaard Nilausen, Lasse Breuning Sluth, Didier Meulien, Christoph von der Goltz, David Nutt, Anne Lingford-Hughes
BACKGROUND: Nalmefene is a µ- and δ-opioid receptor antagonist, κ-opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge...
January 10, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28195139/altered-insula-connectivity-under-mdma
#4
Ishan C Walpola, Timothy Nest, Leor Roseman, David Erritzoe, Amanda Feilding, David J Nutt, Robin L Carhart-Harris
Recent work with noninvasive human brain imaging has started to investigate the effects of 3, 4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap...
February 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28167221/toxicological-evaluation-of-5-methoxy-2-aminoindane-meai-binge-mitigating-agent-in-development
#5
Jakob A Shimshoni, Ilan Winkler, Nir Edery, Ezekiel Golan, René van Wettum, David Nutt
5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28092199/book-reviewsreviews
#6
Márta Virág, Kollár Tamás
Michael S. Gazzaniga, Richard B. Ivry and George R. Mangun Cognitive neuroscience: The biology of the mind (International student edition) (4th ed.) Trevor W. Robbins, Barry J. Everitt and David J. Nutt The neurobiology of addiction Oxford, UK: Oxford University Press, 2010, 318 pp. ISBN: 978-0-1995-6215-2.
March 2016: Journal of Behavioral Addictions
https://www.readbyqxmd.com/read/28042871/acute-d3-antagonist-gsk598809-selectively-enhances-neural-response-during-monetary-reward-anticipation-in-drug-and-alcohol-dependence
#7
Anna Murphy, Liam J Nestor, John McGonigle, Louise Paterson, Venkataramana Boyapati, Karen D Ersche, Remy Flechais, Shankar Kuchibatla, Antonio Metastasio, Csaba Orban, Filippo Passetti, Laurence Reed, Dana Smith, John Suckling, Eleanor Taylor, Trevor W Robbins, Anne Lingford-Hughes, David J Nutt, John Fw Deakin, Rebecca Elliott
Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT)...
April 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27955830/inverse-agonists-what-do-they-mean-for-psychiatry
#8
David Nutt, Stephen Stahl, Pierre Blier, Filippo Drago, Joseph Zohar, Sue Wilson
The nomenclature of drugs is a critical aspect of science, since it can direct research and optimize treatment choices. Traditionally drugs acting on CNS receptors have been classified as either agonists or antagonists. Recently a new class of ligand, the inverse agonist, has been identified in some receptor systems. Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists. Pimavanserin is a new 5-HT2A receptor acting drug that has been given market authorization for psychosis in Parkinson׳s disease...
January 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27909163/psilocybin-for-anxiety-and-depression-in-cancer-care-lessons-from-the-past-and-prospects-for-the-future
#9
EDITORIAL
David Nutt
No abstract text is available yet for this article.
December 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27834755/thirty-years-of-journal-of-psychopharmacology
#10
EDITORIAL
David J Nutt
No abstract text is available yet for this article.
November 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27739164/evidence-for-gaba-a-receptor-dysregulation-in-gambling-disorder-correlation-with-impulsivity
#11
Inge Mick, Anna C Ramos, Jim Myers, Paul R Stokes, Samantha Chandrasekera, David Erritzoe, Maria A Mendez, Roger N Gunn, Eugenii A Rabiner, Graham E Searle, José C F Galduróz, Adam D Waldman, Henrietta Bowden-Jones, Luke Clark, David J Nutt, Anne R Lingford-Hughes
As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [(11) C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity...
October 13, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27705084/levosimendan-for-the-prevention-of-acute-organ-dysfunction-in-sepsis
#12
Anthony C Gordon, Gavin D Perkins, Mervyn Singer, Daniel F McAuley, Robert M L Orme, Shalini Santhakumaran, Alexina J Mason, Mary Cross, Farah Al-Beidh, Janis Best-Lane, David Brealey, Christopher L Nutt, James J McNamee, Henrik Reschreiter, Andrew Breen, Kathleen D Liu, Deborah Ashby
Background Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. Methods We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20)...
October 27, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27703042/the-iccam-platform-study-an-experimental-medicine-platform-for-evaluating-new-drugs-for-relapse-prevention-in-addiction-part-b-fmri-description
#13
John McGonigle, Anna Murphy, Louise M Paterson, Laurence J Reed, Liam Nestor, Jonathan Nash, Rebecca Elliott, Karen D Ersche, Remy Sa Flechais, Rexford Newbould, Csaba Orban, Dana G Smith, Eleanor M Taylor, Adam D Waldman, Trevor W Robbins, Jf William Deakin, David J Nutt, Anne R Lingford-Hughes, John Suckling
OBJECTIVES: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. EXPERIMENTAL DESIGN: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity...
January 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27688219/strengthening-health-systems-while-responding-to-a-health-crisis-lessons-learned-by-a-nongovernmental-organization-during-the-ebola-virus-disease-epidemic-in-sierra-leone
#14
Corrado Cancedda, Sheila M Davis, Kerry L Dierberg, Jonathan Lascher, J Daniel Kelly, Mohammed Bailor Barrie, Alimamy Philip Koroma, Peter George, Adikali Alpha Kamara, Ronald Marsh, Manso S Sumbuya, Cameron T Nutt, Kirstin W Scott, Edgar Thomas, Katherine Bollbach, Andrew Sesay, Ahmidu Barrie, Elizabeth Barrera, Kathryn Barron, John Welch, Nahid Bhadelia, Raphael G Frankfurter, Ophelia M Dahl, Sarthak Das, Rebecca E Rollins, Bryan Eustis, Amanda Schwartz, Piero Pertile, Ilias Pavlopoulos, Allan Mayfield, Regan H Marsh, Yusupha Dibba, Danielle Kloepper, Andrew Hall, Karin Huster, Michael Grady, Kimberly Spray, David A Walton, Fodei Daboh, Cora Nally, Sahr James, Gabriel S Warren, Joyce Chang, Michael Drasher, Gina Lamin, Sherry Bangura, Ann C Miller, Annie P Michaelis, Ryan McBain, M Jana Broadhurst, Megan Murray, Eugene T Richardson, Ted Philip, Gary L Gottlieb, Joia S Mukherjee, Paul E Farmer
An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities...
October 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27650729/neurochemical-binding-profiles-of-novel-indole-and-benzofuran-mdma-analogues
#15
COMPARATIVE STUDY
Jakob A Shimshoni, Ilan Winkler, Ezekiel Golan, David Nutt
3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT2 receptor agonist and monoamine uptake inhibitors determined...
January 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27600363/acute-naltrexone-does-not-remediate-fronto-striatal-disturbances-in-alcoholic-and-alcoholic-polysubstance-dependent-populations-during-a-monetary-incentive-delay-task
#16
Liam J Nestor, Anna Murphy, John McGonigle, Csaba Orban, Laurence Reed, Eleanor Taylor, Remy Flechais, Louise M Paterson, Dana Smith, Edward T Bullmore, Karen D Ersche, John Suckling, Roger Tait, Rebecca Elliott, Bill Deakin, Ilan Rabiner, Anne Lingford-Hughes, David J Nutt, Barbara Sahakian, Trevor W Robbins
There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards...
September 6, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27585792/acute-and-chronic-effects-of-cannabinoids-on-effort-related-decision-making-and-reward-learning-an-evaluation-of-the-cannabis-amotivational-hypotheses
#17
Will Lawn, Tom P Freeman, Rebecca A Pope, Alyssa Joye, Lisa Harvey, Chandni Hindocha, Claire Mokrysz, Abigail Moss, Matthew B Wall, Michael Ap Bloomfield, Ravi K Das, Celia Ja Morgan, David J Nutt, H Valerie Curran
RATIONALE: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. OBJECTIVES: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning...
October 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27581977/packaging-and-prefusion-stabilization-separately-and-additively-increase-the-quantity-and-quality-of-respiratory-syncytial-virus-rsv-neutralizing-antibodies-induced-by-an-rsv-fusion-protein-expressed-by-a-parainfluenza-virus-vector
#18
Bo Liang, Joan O Ngwuta, Richard Herbert, Joanna Swerczek, David W Dorward, Emerito Amaro-Carambot, Natalie Mackow, Barbora Kabatova, Matthias Lingemann, Sonja Surman, Lijuan Yang, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Anne Schaap-Nutt, Peter L Collins, Shirin Munir
Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine/human PIV3 (rB/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced "high-quality" RSV-neutralizing antibodies, defined as antibodies that neutralize RSV in vitro without added complement (B...
November 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27524439/proximity-based-differential-single-cell-analysis-of-the-niche-to-identify-stem-progenitor-cell-regulators
#19
Lev Silberstein, Kevin A Goncalves, Peter V Kharchenko, Raphael Turcotte, Youmna Kfoury, Francois Mercier, Ninib Baryawno, Nicolas Severe, Jacqueline Bachand, Joel A Spencer, Ani Papazian, Dongjun Lee, Brahmananda Reddy Chitteti, Edward F Srour, Jonathan Hoggatt, Tiffany Tate, Cristina Lo Celso, Noriaki Ono, Stephen Nutt, Jyrki Heino, Kalle Sipilä, Toshihiro Shioda, Masatake Osawa, Charles P Lin, Guo-Fu Hu, David T Scadden
Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators...
October 6, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27461515/whole-genome-expression-analysis-reveals-genes-associated-with-treatment-response-to-escitalopram-in-major-depression
#20
Kristi Pettai, Lili Milani, Anu Tammiste, Urmo Võsa, Raivo Kolde, Triin Eller, David Nutt, Andres Metspalu, Eduard Maron
The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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