ICCAM - New drugs for addiction: focus on attenuating core behavioural components of heroin, cocaine and alcohol addiction

Abstract

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; µ-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.

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Duration of the project

3 years

Funding body

Medical Research Council Addiction Cluster award