MARC PhD Callout
PhD Opportunities within MARC
Are you a clinician? Are you looking to undertake a PhD to build your academic career?
The MRC Addiction Research Clinical (MARC) Training scheme has PhD positions available. Please contact us now if you are interested and want to know more – even if you would not want to start until next year or later. We will work with you to develop your project.
The MRC Addiction Research Clinical (MARC) Training programme is led by Prof Anne Lingford-Hughes at Imperial College London, with Prof Colin Drummond at King’s College London and Prof Matt Hickman at University of Bristol. The vision of the MARC programme is to develop the future UK clinical research leaders in addiction to build and sustain capacity in this vital area of clinical neuroscience and address the gap in clinical research capacity in the addictions field in the UK. MARC can support clinicians (eg psychiatrists, psychologists etc) to undertake a PhD to train in a range of research approaches and techniques to effectively translate basic and epidemiological evidence into the clinical environment using early (T1, T2) experimental medicine studies in patients for the benefit of clinical populations and their treatment.
For more information contact the MARC Team email@example.com or contact the MARC leads directly Anne Lingford-Hughes (Imperial College London), Colin Drummond (King's College London) or Matthew Hickman (University of Bristol).
Imperial College Contacts
|Who||Area of Expertise|
|Professor Anne Lingford-Hughes (MARC Lead)||Neuroimaging, pharmacology, clinical trials, experimental firstname.lastname@example.org|
|Professor David Nutt||Pharmacology, experimental medicine, email@example.com|
|Dr Jim Myers||PET neuroimaging firstname.lastname@example.org|
|Professor David Sharp||Brain inflammation, traumatic brain injury, email@example.com|
|Dr Henrietta Bowden-Jones||Lead clinician for National Gambling Clinic, firstname.lastname@example.org|
|Dr Tony Goldstone||Endocrinology, appetite and eating behaviours, cognitive assessment, email@example.com|
|Please see below for potential projects|
Imperial College potential project areas
Characterizing the neurobiology of key brain processes in addiction and their neuropharmacological modulation.
(Lingford-Hughes, Nutt, Goldstone, Sharp). The MRC ICCAM platform study was set up to investigate the effects of alcohol, opioid and cocaine dependence on brain function and structure & to examine the modulatory effects of current and potential medication. Its database contains 1. structural, DTI, fMRI (monetary incentive delay task; go-nogo; evocative images), resting state MR; 2. 4 sessions of the fMRI tasks with placebo, naltrexone, DRD3 antagonist, NK1 antagonist; 3. clinical and neurocognitive assessments. Potential projects include: Does DRD3 antagonism preferentially impact on circuitry underlying reward compared with impulsivity? How does NK1 antagonism alter the relationship between fMRI task activity and resting state; The relationship between cognitive performance & white matter integrity.
Do appetitive gut hormones attenuate core behavioural components of addiction as new targets to prevent relapse in nicotine and alcohol dependence
(Goldstone, Nutt, Lingford-Hughes). This recently started study uses the ICCAM platform to investigate the hypothesis that suppressing/antagonising ghrelin or GLP-1 attenuates core behavioural components of addiction. This project may may lead to novel relapse prevention pharmacotherapies and provides exceptional training in fMRI.
GABA-B receptor function in addiction
(Lingford-Hughes, Nutt, Bowden-Jones). Interest in the role of the GABA-B receptor in addiction has been increasing with evidence that the GABA-B agonist, baclofen, can prevent relapse in alcoholism and has potential in treating other addictions. Currently there is a debate about the appropriate dose and evidence to guide appropriate dosing is limited. This study employs a range of objective measures (EEG, eye movements) with blood sampling to provide PK-PD evidence to inform prescribing in addiction to alcohol, opiate or pathological gambling.
Improving GHB withdrawal with baclofen
(NIHR RfPB funded; Lingford-Hughes). GHB withdrawal can be difficult to manage and may result in hospital admission. The GABA-B agonist, baclofen has become increasingly popular with anecdotal evidence that it reduces GHB withdrawal severity. This feasibility study will optimize recruitment and assessment of baclofen in GHB withdrawal to underpin an RCT.
Measuring dopamine D3 receptor in alcoholism (11C-PHNO PET, fMRI)
(Lingford-Hughes, Myers,Sharp). 11C-PHNO PET measures DRD3 availability and we have shown increased DRD3 in hypothalamus in alcoholism. This project will investigate the association between this increase and reward sensitivity measured with fMRI. This dataset can also be compared with ongoing 11C-PHNO PET study in traumatic brain injury (Sharp) since alcohol misuse and traumatic brain injury commonly co-exist.
Neurotransmitters in Opiate and Alcohol Addiction.
(Lingford-Hughes, Nutt, Myers, Goldstone, Bowden-Jones). PET imaging data is available to examine the neuropharmacology (dopamine, GABA, opiate) of alcohol and opiate addiction and pathological gambling (PG) – both receptor availability and changes in endogenous neurotransmitter levels. Combined with ICCAM MR protocol, our current and accruing database provides an exceptional resource to investigate the neurobiology of addiction with measures of receptor availability and function. Projects include exploring the relationship between opiate and/or GABA systems and MR (rsfMRI, fMRI) in PG or alcoholism; Comparing PG with substance addiction in these measures; Exploring the dopamine, opioid and GABA systems and impulsivity in these groups; Investigating the relationship between opioid, GABA and dopamine receptor availability in heath and addiction.
King's College Contacts
|Who||Area of Expertise|
|Professor Colin Drummond (MARC Lead)||Alcohol clinical and experimental firstname.lastname@example.org|
|Professor John Strang||Drugs clinical and experimental research||John.Strang@kcl.ac.uk|
|Professor Gunter Schumann||Addiction biology, genetics, brain mechanisms of email@example.com|
|Professor John Marsden||Psychology of Addiction, experimental studies, clinical firstname.lastname@example.org|
|Professor Michael Lynskey||Genetic and environmental influences on addiction, twin email@example.com|
|Professor Ann McNeil||Tobacco addiction, psychology of addiction, tobacco control firstname.lastname@example.org|
|Professor Hilary Little||Psychopharmacology, basic and human email@example.com|
|Please see below for potential projects|
King's College London Potential Project Areas
Influence of early experience on alcohol reinforcement and the hypothalamo-pituitary-adrenal system in heavy and light drinkers.
(Drummond, Little). Many alcoholics have experienced emotional, physical or sexual trauma in early life, but the physiological mechanisms not yet understood. Such experiences also affect the functioning of the hypothalamo-pituitary-adrenal system (HPA). The project will examine the influence of early trauma on responses to alcohol priming and alcohol-related cues, plus HPA reactivity and HPA feedback control in heavy and light alcohol drinking volunteers. The project will provide both valuable data concerning alcohol reinforcement and experience in clinical and laboratory research.
Alcohol-induced harm in adolescent brain development and its consequences for mental health.
(Schumann, Drummond). The overall aims are to identify alcohol-induced brain dysfunction and establish its relation to cognition, behaviour and mental health. We will characterise the impact of alcohol exposure on adolescent brain function and structure, and neuropsychological performance and investigate compounding environmental or genetic factors which increase or protect against alcohol-induced harm or risk for abuse. We will enrich and analyse the IMAGEN cohort (www.imagen-europe.com). A longitudinal MRI design will allow study of the interaction between alcohol consumption, genetic factors, brain morphology and function.
Cognitive processing in addictive behaviours and novel therapy for craving control.
(Marsden, Drummond). Advances in cognitive therapies for anxiety & trauma disorders show that stressful memories can be re-consolidated to reduce the sense of current threat. In addiction, attention and implicit cognitions highlight triggers for substance urges & related beliefs. Adapting memory-focused cognitive therapy could help patients to control craving and unhelpful evaluations. The effects of memory-focused and craving control interventions on craving and cognitive processing will be characterized to identify active ingredients of the interventions to develop a novel cognitive therapy for stimulant, opioid and alcohol use disorders.
Early phase clinical trial of varenicline in patients with severe mental illness (SMI).
(McNeill, Drummond). Smoking in SMI patients is a major public health problem however evidence based interventions for smoking cessation is limited since most clinical trials of medications to aid smoking cessation exclude such patients. This will be an early phase double blind RCT of varenicline versus placebo in SMI patients which will study mechanisms of action of the drug on nicotine craving, psychiatric symptoms and smoking cessation rates.
Experimental study of the effect of acamprosate and nalmefene on the protracted alcohol withdrawal syndrome.
(Drummond, Little). Acamprosate and nalmefene are effective in preventing relapse in some alcohol dependent patients. Improved understanding of their mechanisms of action will inform development and better targeting of relapse prevention medication. Little is known about pharmacotherapy for the protracted alcohol withdrawal syndrome (PAWS) which is a significant predictor of relapse. Experimental medicine studies will examine the effects of medications during post-acute withdrawal period.
Experimental testing of cue-reactivity to drug stimuli of former heroin/opioid addicts under naltrexone blockade.
(Strang, Marsden, Drummond). Translational experimental medicine study of the effects of a naltrexone implant on opiate craving and cue reactivity will be conducted in the context of a funded placebo controlled trial. The study will include subjective, physiological and fMRI measures of cue reactivity to identify the mediational effects of naltrexone on cue reactivity and relapse to opiate use.
Independent and interactive effects of psychosocial and genetic risk factors on treatment outcome in the addictions.
(Lynskey, Drummond). Despite limited success in identifying gene variants associated with the development of alcohol and other substance dependence, twin and family studies indicate that there is a strong genetic component to risks for these disorders. Identifying variants associated with later stages in drug dependence trajectories (remission, relapse) may provide more promising targets for intervention (e.g., drug development). This project would examine whether gene variants and gene systems previously identified as being associated with alcohol/ drug dependence are associated with treatment outcome and whether any such associations are consistent across, or interact with, indicators of psychosocial risk.
University of Bristol Contacts
|Who||Area of Expertise|
|Professor Matt Hickman (MARC Lead)||Public health and addiction firstname.lastname@example.org|
|Professor Marcus Munafo||Experimental Psychology, genetics of alcohol and tobacco.||Marcus.Munafo@bristol.ac.uk|
|Professor Stan Zammit||Clinical Epidemiology and genetic epidemiology of psychiatric disorders||Stan.Zammit@bristol.ac.uk|
|Dr Tim Williams||Addiction psychiatry and psychopharmacology||Tim.Williams@bristol.ac.uk|
|Professor Graeme Henderson||Heroin addiction, opioid tolerance, psychopharmacology||Graeme.Henderson@bristol.ac.uk|
|Dr Emma Robinson||Psychopharmacology||Emma.S.J.Robinson@bristol.ac.uk|
|Professor Caroline Relton||Genetic & Epigenetic Epidemiology||Caroline.Relton@bristol.ac.uk|
|Professor Kate Tilling||Medical Statistics, Causal Modelling, Longitudinal Modelling incl epigenetic data||Kate.Tilling@bristol.ac.uk|
|Professor John Macleod||Primary care and addiction epidemiology, record linkage||John.MacLeod@bristol.ac.uk|
|Please see below for potential projects|
University of Bristol potential project areas
Emotional changes and addiction: animal and experimental models
(Robinson, Hickman, Munafo). The direction and inter-relationship between depressive symptoms and addiction is complex, with epidemiological studies often providing weak evidence and unable to tease out direction of effect. Novel translational behavioural models have been developed that replicate symptoms associated with cognitive affective behaviour and responses to emotional stimuli. These will be used alongside pharmacology and genetic approaches to manipulate specific neural and neurochemical processes to test specific hypotheses relating to the relationship between depression and addiction.
Impact of substance use on psychopathology and functioning using the ALSPAC birth cohort and Swedish record linkage cohorts
(Zammit, Hickman, Munafo; linked to MRC grant on “Pathways to Psychosis). Strong evidence for an association between cannabis and schizophrenia stems from the Swedish Conscript Cohort. Recent analyses of ALSPAC, however, suggest a stronger signal between heavy tobacco use and psychotic like symptoms. The project will undertake epidemiological and genetic analyses across multiple cohorts (including ALSPAC, Swedish record linkage cohorts, Imagen, Biobank, Psychiatric Genetics Consortium data) to establish and use genetic markers of substance use and to test and contrast evidence for a causal association between cannabis and tobacco on psychotic illness.
Incorporating epigenetic measures as biomarkers of risk prediction in pathways to addiction
(Relton, Hickman, Zammit; MRC IEU).There are multiple pathways to addiction, including foetal exposure to substances, early family adversity through externalising problems to addiction in late adolescence/ and young adulthood. ALSPAC provides the opportunity to investigate these pathways combining epidemiological and epigenetic approaches, including DNA methylation as a biomarker of substance use and assessing evidence for epigenetic antecedents in relation to prior exposures of later substance.
Mechanism, effects and impact of poly-drug use and opiate use on euphoria and respiratory depression – animal and epidemiological models
(Henderson, Hickman, Williams; NIH, MRC funded “Mechanisms of Ethanol's Reversal of Opioid Tolerance”). Epidemiological data suggest that alcohol and opiate use are associated with an increased risk of fatal overdose compared to opiate use only. The assumption of a multiplicative relationship between the two drugs on respiratory depression is not supported by our finding that acute alcohol use may remove tolerance to heroin use. Other drugs and opioids may interact in different ways. European forensic and epidemiological data will identify the commonest forms of polydrug use involving heroin and other opioids, which will then be investigated in a series of animal experiments to establish mechanism of interaction, and to inform overdose prevention.
Morbidity and mortality amongst opiate users and the ameliorating effect of care interventions
(Macleod, Hickman, Tilling). Large observational studies are required to investigate the impact of specialist drug treatment on reducing mortality risk and improving health of the population. In collaboration with the Farr Institute national data linkage studies in South West England, Wales, and Scotland will be established to create multiple natural experiments that than test and identify how best to deliver specialist drug in the community and prison in order to reduce mortality and morbidity. The project is linked to MRC Centre for the Improvement of Population Health through E-health Research (CIPHER).
What is the relationship between adolescent alcohol use and mental health outcomes in young adulthood: epidemiological and experimental analyses
(Hickman, Munafo, Tilling). There is growing concern that heavy episodic drinking in adolescence could lead to impairments in cognitive function and emotional processing in young adulthood. In this project, linked to recent MRC grant on Alcohol and ALSPAC and MRC IEU, we propose to investigate whether frequent binge drinking is associated with relatively poor cognitive and emotional processing, and impulsivity compared to lower risk drinkers. And whether there is a stronger association between poor cognitive and emotional processing and impulsivity and early-onset binge drinking compared to late-onset binge drinking?