fmri studies of addiction and relapse Rebecca Elliott Bill Deakin Anna Murphy Neuroscience and Psychiatry Unit

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1 fmri studies of addiction and relapse Rebecca Elliott Bill Deakin Anna Murphy Neuroscience and Psychiatry Unit

2 Background Previous PhD projects on brain basis of craving: Lesley Peters and Dan Lubman Expertise in functional imaging of relevant emotional and motivational processes (reward, impulsivity) MRC programme grant in ASPD (Deakin, Dolan, Anderson, Williams, Elliott) MRC addiction research strategy Small (<300K) proof of principle grants Attracting new researchers to addiction Addiction clusters T1 priority theme: Developing preventive strategies and new treatments for addiction and relapse ICCAM cluster (with Imperial College/Cambridge)

3 Neurobiology of Craving Study (NOCS) Rebecca Elliott, Bill Deakin, Ian Anderson Prunwat Bijral, Lesley Peters Anna Murphy Aim: to investigate the brain mechanisms of craving and cognition in detoxified opiate addicts and their relationship to relapse liability

4 Daglish et al (2001) Abstinent opiate addicts Slides of drug paraphenalia ACC response to craving cues ACC is key cognitive-emotional Interface.

5 Key questions How does the brain response to craving develop over time? Do detoxified addicts show abnormal brain responses associated with impulsivity and attentional bias (important cognitive mechanisms for addictive behaviour)? How are these responses modulated by current craving state? Which of these factors are associated with relapse?

6 Patients Inpatients from Chapman Barker Unit Tested after heroin detoxification, methadone stabilisation and lofexidine reduction Sessions within few days before discharge Follow up telephone screening to assess relapse

7 Design Craving video, tasks 15 controls Counterbalanced order Neutral video, tasks Craving video, tasks Approx 25 patients Relapse within 3 months 40 patients Counterbalanced order Neutral video, tasks Approx 15 patients No relapse within 3 months

8 Issues Research governance. Developing a craving video. Great interest from patients. Problems with drop-out, comorbidities etc. 6/40 scanned so far. Will relapse rates allow a relapse vs. nonrelapse comparison?

9 ICCAM cluster Collaboration with Imperial College, University of Cambridge and GSK Approx 2 million over 3 years Establishing and testing an experimental platform for testing new drugs in addiction Preclinical component plus neuropsychology and fmri in clinical populations

10 Aims To measure reinforcement, inhibition and stress responses in alcohol, opioid and cocaine dependence using fmri in 24 subjects per group + 36 controls To assess the effect of acute steady state Naltrexone (µ-opioid antagonist), GSK (D3 selective dopamine antagonist), and Vofopitant (NK1 antagonist) treatment versus placebo in a 4-way randomised doubleblind design in all individuals. To identify putative predictors of relapse by performing 3, 6 and 12 months behavioural follow-up. To establish power/effect size to accurately power future acute and steady-state pharmacological studies in these clinical populations.

11 Design Screening and initial assessment Full baseline testing including fmri Go/NoGo test of behavioural inhibition Reward task Stress response task 4 further visits on each treatment plus placebo Randomised, counterbalanced

12 Bjork et al (2008) Substance dependent patients (primarily alcohol): abnormal reward and loss processing

13 Issues ICCAM study requires 5 intensive sessions plus follow-up: will need to recruit highly motivated and stable people Recruiting 2 weeks-6 months after detox ICCAM study requires recruiting people with (relatively) pure addictions: feasibility?

14 Contacts Rebecca Elliott: Bill Deakin: Anna Murphy:

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