Publications
324 results found
Lingford-Hughes A, 2015, AN FMRI STUDY OF NALMEFENE ON ALCOHOL EFFECTS IN REWARD ANTICIPATION IN ALCOHOL DEPENDENCE, ALCOHOL AND ALCOHOLISM, Vol: 50, ISSN: 0735-0414
Lingford-Hughes A, 2015, IMAGING THE NEUROPHARMACOLOGY OF ALCOHOLISM, ALCOHOL AND ALCOHOLISM, Vol: 50, ISSN: 0735-0414
Lingford-Hughes A, Kalk N, Guo Q, et al., 2015, INVESTIGATING ALCOHOL AND NEUROINFLAMMATION, ALCOHOL AND ALCOHOLISM, Vol: 50, ISSN: 0735-0414
Lingford-Hughes A, 2015, AN FMRI STUDY OF NALMEFENE ON ALCOHOL EFFECTS IN REWARD ANTICIPATION IN ALCOHOL DEPENDENCE, ALCOHOL AND ALCOHOLISM, Vol: 50, ISSN: 0735-0414
Lingford-Hughes A, Daglish M, 2015, Drugs of abuse, Fundamentals of Clinical Psychopharmacology: Fourth Edition, Pages: 143-161, ISBN: 9781498718943
Paterson LM, Flechais RSA, Murphy A, et al., 2015, The Imperial College Cambridge Manchester (ICCAM) platform study: an experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: study description, Journal of Psychopharmacology, Vol: 29, Pages: 943-960, ISSN: 1461-7285
Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.
Turton S, Durant C, Wilson S, et al., 2015, GABA-B receptor function in healthy volunteers, a pharmacokinetic and pharmacodynamic study of two doses of baclofen compared to placebo
AIMS AND HYPOTHESISTo assess the subjective and objective effects of baclofen on brain function in healthy volunteers. BACKGROUNDRecent evidence suggests baclofen, a γ-aminobutyric acid type B (GABA-B) receptor agonist, reduces alcohol consumption and craving and promotes abstinence in alcoholics. However, characterisation of the GABA-B receptor system in clinical addiction is limited, and it is unclear why some patients require, or tolerate, higher doses to treat alcoholism. This study assesses the effects of baclofen on brain function in healthy volunteers to inform future studies investigating the sensitivity of GABA-B receptors in alcohol addiction. METHODSEight healthy male volunteers completed a double blind randomised 3-way cross over study, receiving oral placebo (vitamin C 100mg), 10mg and 60mg baclofen. Subjective and objective measurements were taken at baseline (before medication) and at +30mins, 1, 2, 3, 4 and 6 hours after dosing. Objective measures included blood plasma samples, heart rate and blood pressure. Subjective measures included; the Subjective High Assessment Questionnaire (SHAS), visual analogue scales for sleepy, relaxed, tense and alert and a motor coordination task (zig-zag task). Pharmacokinetic data was obtained using liquid chromatography mass-spectrometry (LC-MS) to measure plasma baclofen concentrations.RESULTS60mg Baclofen showed changes in subjective measures peaking at 2 hours post dosing compared with placebo, including a significant increase (p<0.05) in total SHAS scores with individual items, including feeling ‘drunk or intoxicated’, effects of alcohol and ‘muddled or confused’ particular affected.. Systolic blood pressure was significantly increased (p<0.05) at the 2 hours post 60mg dose. For both 10mg and 60mg baclofen, peak plasma concentration was achieved 60 minutes post dose. Pharmacokinetic data will be presented. There were no significant changes in these measures between 10mg Baclof
Savulich G, Ersche KD, Deakin B, et al., 2015, The modulatory effects of naltrexone on the underlying neural network in alcohol and drug dependence: an FMRI study, 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism, Publisher: Wiley, Pages: 253A-253A, ISSN: 0145-6008
Nutt DJ, Lingford-Hughes A, Erritzoe D, et al., 2015, The dopamine theory of addiction: 40 years of highs and lows, NATURE REVIEWS NEUROSCIENCE, Vol: 16, Pages: 305-312, ISSN: 1471-003X
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- Citations: 339
Taylor EM, Murphy A, Ersche KD, et al., 2015, Neuropsychological, self-report and neurocognitive measures of impulsivity in substance-dependent individuals compared to controls, ECNP Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S85-S86, ISSN: 0924-977X
Lingford-Hughes A, Nestor L, 2015, Neuroscience perspectives on addiction: Overview, Handbook of Neuroethics, Pages: 999-1024, ISBN: 9789400747067
Substance addiction can be a chronic relapsing disorder. While different drugs of addiction have different primary molecular targets, it has been demonstrated that many share the common action of being able to increase dopamine within hardwired reward circuitry. While this effect is widely conceived as a primary factor driving initial drug use, long-term adaptations within this hard-wired neural circuitry underlie the transition from drug use to drug dependence. Significantly, these neuroadaptations are responsible for triggering recurrent drug relapse in people recovering from addiction, even when following periods of long-term abstinence. While there is no animal model of addiction that can fully emulate the human condition, some animal models do permit the investigation of specific elements of drug addiction, particularly those involving the reward system and its role in drug-seeking behavior. Neuroimaging methods now also permit us to test hypotheses of addiction derived from such animal models, allowing the field of neuroscience to examine neural components of drug abuse and dependence in humans. These neuroimaging procedures permit neuroscientists to test hypotheses in humans at different stages of the addiction cycle, particularly with a view to developing better treatments.
Quelch D, De Santis V, Strege A, et al., 2015, Influence of Agonist Induced Internalization on [<SUP>3</SUP>H]Ro15-4513 Binding-An Application to Imaging Fluctuations in Endogenous GABA With Positron Emission Tomography, SYNAPSE, Vol: 69, Pages: 60-65, ISSN: 0887-4476
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- Citations: 8
Nutt D, Wilson S, Lingford-Hughes A, et al., 2015, Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: A study in healthy volunteers, NEUROPHARMACOLOGY, Vol: 88, Pages: 155-163, ISSN: 0028-3908
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- Citations: 27
Mick I, Myers J, Stokes PRA, et al., 2014, Amphetamine induced endogenous opioid release in the human brain detected with [<SUP>11</SUP>C]carfentanil PET: replication in an independent cohort, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 17, Pages: 2069-2074, ISSN: 1461-1457
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- Citations: 37
Gell L, McLeod J, Holmes J, et al., 2014, Reflections and best practice recommendations for interdisciplinary working: a case study on the identification of the determinants of addiction from the Addiction and Lifestyles In Contemporary Europe Reframing Addictions Project (ALICE RAP), European Public Health Science Conference, Publisher: ELSEVIER SCIENCE INC, Pages: 13-13, ISSN: 0140-6736
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- Citations: 1
Watson BJ, Taylor LG, Reid AG, et al., 2014, Investigating expectation and reward in human opioid addiction with [<SUP>11</SUP>C]raclopride PET, ADDICTION BIOLOGY, Vol: 19, Pages: 1032-1040, ISSN: 1355-6215
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- Citations: 21
Stokes PRA, Myers JF, Kalk NJ, et al., 2014, Acute increases in synaptic GABA detectable in the living human brain: A [<SUP>11</SUP>C]Ro15-4513 PET study, NEUROIMAGE, Vol: 99, Pages: 158-165, ISSN: 1053-8119
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- Citations: 37
Mick I, Myers J, Stokes P, et al., 2014, Endogenous opioid release in pathological gamblers after an oral amphetamine challenge: a [<SUP>11</SUP>C]carfentanil PET study, 27th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S699-S700, ISSN: 0924-977X
Lingford-Hughes A, 2014, Experimental human evidence for a role of the opioid system in alcohol dependence, 27th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S760-S760, ISSN: 0924-977X
Myers JFM, Evans CJ, Kalk NJ, et al., 2014, Measurement of GABA Using J-Difference Edited <SUP>1</SUP>H-MRS Following Modulation of Synaptic GABA Concentration with Tiagabine, SYNAPSE, Vol: 68, Pages: 355-362, ISSN: 0887-4476
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- Citations: 25
Crawford MJ, Sanatinia R, Barrett B, et al., 2014, The clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial, Sexually Transmitted Infections, Vol: 91, Pages: 37-43, ISSN: 1472-3263
Objectives To examine the clinical and costeffectivenessof brief advice for excessive alcoholconsumption among people who attend sexual healthclinics.Methods Two-arm, parallel group, assessor blind,pragmatic, randomised controlled trial. 802 people aged19 years or over who attended one of three sexualhealth clinics and were drinking excessively wererandomised to either brief advice or control treatment.Brief advice consisted of feedback on alcohol and health,written information and an offer of an appointment withan Alcohol Health Worker. Control participants receiveda leaflet on health and lifestyle. The primary outcomewas mean weekly alcohol consumption during theprevious 90 days measured 6 months afterrandomisation. The main secondary outcome wasunprotected sex during this period.Results Among the 402 randomised to brief advice,397 (99%) received it. The adjusted mean difference inalcohol consumption at 6 months was −2.33 units perweek (95% CI −4.69 to 0.03, p=0.053) among thosein the active compared to the control arm of the trial.Unprotected sex was reported by 154 (53%) of thosewho received brief advice, and 178 (59%) controls(adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496).There were no significant differences in costs betweenstudy groups at 6 months.Conclusions Introduction of universal screening andbrief advice for excessive alcohol use among peopleattending sexual health clinics does not result inclinically important reductions in alcohol consumption orprovide a cost-effective use of resources.
Erritzoe D, Tziortzi A, Bargiela D, et al., 2014, <i>In Vivo</i> Imaging of Cerebral Dopamine D3 Receptors in Alcoholism, NEUROPSYCHOPHARMACOLOGY, Vol: 39, Pages: 1703-1712, ISSN: 0893-133X
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- Citations: 43
Kalk NJ, Guo Q, Owen DR, et al., 2014, HIPPOCAMPAL MICROGLIAL DYSFUNCTION IN ALCOHOL DEPENDENCE: A [C-11]PBR28 POSITRON EMISSION TOMOGRAPHY (PET) STUDY, 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA), Publisher: WILEY-BLACKWELL, Pages: 23A-23A, ISSN: 0145-6008
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- Citations: 1
Lingford-Hughes A, 2014, IMAGING GABA-BENZODIAZEPINE RECEPTORS WITH 11C-R015 4513 PET, 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA), Publisher: WILEY-BLACKWELL, Pages: 316A-316A, ISSN: 0145-6008
Crawford MJ, Sanatinia R, Barrett B, et al., 2014, The clinical effectiveness and cost-effectiveness of brief intervention for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial (SHEAR), HEALTH TECHNOLOGY ASSESSMENT, Vol: 18, Pages: 1-+, ISSN: 1366-5278
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- Citations: 12
Stokes PRA, Benecke A, Puraite J, et al., 2014, Does human presynaptic striatal dopamine function predict social conformity?, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 28, Pages: 237-243, ISSN: 0269-8811
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- Citations: 4
Mick I, Myers J, Stokes P, et al., 2014, Endogenous opioid release in pathological gamblers after an oral amphetamine challenge: a [<SUP>11</SUP>C]carfentanil PET study, ECNP Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S62-S63, ISSN: 0924-977X
Kalk NJ, Lingford-Hughes AR, 2014, The clinical pharmacology of acamprosate, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Vol: 77, Pages: 315-323, ISSN: 0306-5251
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- Citations: 52
Kalk NJ, Owen DR, Tyacke RJ, et al., 2013, Are Prescribed Benzodiazepines Likely to Affect the Availability of the 18 kDa Translocator Protein (TSPO) in PET Studies?, SYNAPSE, Vol: 67, Pages: 909-912, ISSN: 0887-4476
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- Citations: 16
Orban C, McGonigle J, Kalk NJ, et al., 2013, Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients, AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE, Vol: 39, Pages: 433-440, ISSN: 0095-2990
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- Citations: 13
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