New drugs for addiction: focus on attenuating core behavioural components of heroin, cocaine and alcohol addiction
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
Addiction to drugs such as heroin, cocaine and alcohol are a major problem in our society and globally. Is it possible to understand the processes that lead to addiction and to develop drugs that can be used for treatment? These are the two major questions that motivate the ICCAM addictions research cluster and this application. The ICCAM cluster brings together clinical and preclinical researchers from Imperial College London, Cambridge and Manchester Universities to address the problem of drug development for addiction. We seek to identify rational potential targets for drug development based upon our understanding of the pharmacology and brain processes engaged in addiction, rather than a random ?shotgun? approach. As a society, many think of addiction to drugs such as heroin, cocaine and alcohol as individual conditions with underlying social causes. This may not be the case with the established clinical condition, and this point of view may have impeded rational drug development for these disorders. The ICCAM cluster has identified multiple potential therapeutic drugs that may be of use in the treatment of addiction and now seeks to develop a ?platform? to rapidly assess their efficacy in humans. The word ?platform? means that we will adopt a common research approach based at each of our three sites to study the effects of particular drugs in human participants on processes that are relevant to addiction. We will use state of the art brain imaging techniques to study the effect of drugs on brain activity while a person responds to rewards, for example. These will be combined with neuropsychological assessment and monitoring of clinical outcomes to develop our research capacity.
Technical Summary
Substance Use Disorders are of large and growing prevalence and carry substantial morbidity, mortality and public costs, yet pharmacotherapy is at an early stage of development. While social context, public health policy and psychological approaches are clearly relevant to development and treatment of addiction they are of both limited efficacy and specificity, underlining the need for pharmacotherapy. Despite the proven utility of some drug interventions for addiction [eg methadone, buprenorphine, naltrexone for heroin dependence and acamprosate and naltrexone for alcohol dependence] many patients do not respond. There are no proven pharmacotherapies for cocaine. There is a pressing need to develop novel pharmacotherapies acting across a broader range of components of addictive processes. To this end, there have been major advances in recent years in the understanding of the neurobiology of addiction which offers a new approach to identifying drug targets based on brain mechanisms. Our cluster will use a new experimental medicine research ?platform? and work with new potential drug treatments provided in part by our industrial stakeholder GlaxoSmithKline [GSK]. This initial cluster application develops a platform to assess candidate brain systems underpinning relapse at molecular, network and behavioural levels by assessing three high-likelihood, theoretically critical, target mechanisms comprising: dopamine DRD3 receptors, for relapse prevention primarily by reducing cue-reactivity/craving and impulsivity; ?-opioid receptors, which mediate the reinforcing effects of opioids and are also implicated in impulsivity and hence relapse, especially under conditions of stress; and NK1 receptors, implicated in both stress and reward responses. These drugs will be assessed with novel psychological and fMRI paradigms in human alcohol, heroin and cocaine addicts and in parallel preclinical studies. The platform will then be available for the study of other candidate treatment approaches for addiction that may include for example orexin antagonists and appetite regulating peptides.
Publications

Aubin HJ
(2015)
Clinical relevance of as-needed treatment with nalmefene in alcohol-dependent patients.
in European addiction research

Caprioli D
(2015)
Dissociable rate-dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum.
in The Journal of neuroscience : the official journal of the Society for Neuroscience

Caprioli D
(2013)
Baseline-dependent effects of cocaine pre-exposure on impulsivity and D2/3 receptor availability in the rat striatum: possible relevance to the attention-deficit hyperactivity syndrome.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Colasanti A
(2011)
Opioids and anxiety.
in Journal of psychopharmacology (Oxford, England)


Hart MG
(2017)
Advanced magnetic resonance imaging and neuropsychological assessment for detecting brain injury in a prospective cohort of university amateur boxers.
in NeuroImage. Clinical

Hayes A
(2020)
P.331 The relationship between reward processing and impulsivity in addiction: a functional magnetic resonance imaging study
in European Neuropsychopharmacology

Hayes DJ
(2014)
Brain ?-aminobutyric acid: a neglected role in impulsivity.
in The European journal of neuroscience

McGonigle J
(2017)
The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.
in Journal of psychopharmacology (Oxford, England)

Mitchell F
(2017)
Anne Lingford-Hughes: to get into addiction, just say yes.
in The lancet. Psychiatry
Description | Heptares Therapeutics Ltd |
Amount | £528,093 (GBP) |
Organisation | P1vital Consortium |
Sector | Private |
Country | United Kingdom |
Start | |
End | 03/2017 |
Description | ICCAM cluster (Cambridge site) |
Amount | £413,162 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2011 |
End | 07/2013 |
Title | addiction brain provocation tests |
Description | 3 fmri exposure paradigms to probe stress impulsivity and rewards sensitivity developed and validated |
Type Of Material | Model of mechanisms or symptoms - human |
Provided To Others? | No |
Impact | useful platform technology |
Description | link with GSK |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | this is a shared project with the PET analaysi team at GSK Uk in the clinical imaging centre |
Collaborator Contribution | help in data acquisition and analysis |
Impact | several abstract presentations at intrnational PET meetings |
Start Year | 2009 |
Description | Disseminating information about the MARC scheme |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Presented MARC scheme, its aims and opportunities. Presented at RCPsych Addictions Faculty Meeting 2016 as well as other regional meetings alongside presentation of research outputs from other grants |
Year(s) Of Engagement Activity | 2015,2016 |
URL | http://www.imperial.ac.uk/medicine/mrc-addiction-research-clinical-training/ |
Description | MRC Summer school, Cardiff Neuroscience |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Speaker at MRC Centre for Neuropsychiatric Genetics and Genomics Summer School in Brain Disorder Research: https://www.cardiff.ac.uk/medicine/news/remedy/27/mrc-cngg-summer-school Cover neurobiology of addiction and its treatment. Promote MARC scheme to delegates. |
Year(s) Of Engagement Activity | 2015,2017,2018 |