Neural correlates of reward and emotion in opiate dependence (NCORE)
Research type
Research Study
Full title
Characterising the neurobiology of detoxification and early abstinence in opiate addiction: is there a role for NK1 antagonism to improve outcomes? A double-blind, placebo controlled proof-of-concept study of acute NK1 antagonism on neural correlates of reward and emotional processing in opioid dependence before and after methadone detoxification.
IRAS ID
262604
Contact name
Anne Lingford-Hughes
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Research Summary
Opiate addiction is a major health challenge facing the UK, with numbers of opiate-related deaths rising to record levels. Opiate substitution medication (e.g. methadone) and psychosocial support are effective, but there is now an increasing focus on achieving abstinence. Many addicts desire abstinence but find it hard to achieve and maintain. The effectiveness of current medications is limited, so we are in need of new treatments. We believe that understanding brain processes such as reward and emotional processing will inform development of improved treatments. There is evidence from preclinical and human data suggesting that NK1 receptor antagonism represents a therapeutic target worthy of further exploration in this population.
We will use an established experimental approach to conduct a randomised, placebo-controlled study of a single dose of aprepitant (an NK1 receptor antagonist) in opiate dependent individuals towards the end of their community based detoxification from methadone, and again within a few weeks of abstinence.
Participant will complete fMRI scans to assess brain responses to reward anticipation, processing of negative images and also opiate-related cues. We will assess subjective (how they feel) and objective (how they perform) impact of lab-based tasks that involve processing of reward and of positive and negative emotional stimuli. Participants will take their daily methadone, then be randomly allocated to receive placebo or aprepitant before completing the MR protocol and cognitive tasks. On their 2nd visit at least a week later, they will take the other medication and complete the same study tasks. We will also measure whether aprepitant moderates any subjective (e.g. liking) or objective (e.g. breathing) effects. In their first few weeks of abstinence, they will return to complete the two study days again, though without taking methadone. Participants will be followed up for 1 year to monitor clinical outcomes and relapse.Summary of Results
This study was titled “Neural correlates of reward and emotion in opiate dependence (NCORE)- Characterising the neurobiology of detoxification and early abstinence in opiate addiction: is there a role for NK1 antagonism to improve outcomes? A double-blind, placebo-controlled proof-of-concept study of acute NK1 antagonism on neural correlates of reward and emotional processing in opioid dependence before and after methadone detoxification”.
The research was carried out by Imperial College London and funded by the Medical Research Council. 80 participants took part in the study. 53 participants were opioid dependent and maintained on methadone, and 27 participants were healthy volunteers. The study took place at the Hammersmith Hospital in White City in London from October 2019 to January 2024. The research was conducted with the purpose of improving treatment outcomes for methadone detoxification and relapse prevention in opioid dependence.
We wanted to find out whether the medicine aprepitant could be helpful for this. We used brain imaging technology to detect changes in brain activation whilst the participants performed different psychological tasks. There were three tasks used to investigate how brain function may differ in opioid dependence compared with healthy volunteers. We used a cue reactivity task to examine brain responses to drug-related images; a monetary reward task to examine brain responses to natural rewards; and an aversive images task to examine brain responses to negative stimuli like injury or threat.
Compared with healthy volunteers, we found that the methadone group had higher brain responses to drug cues, lower brain responses to monetary rewards, and lower brain responses to aversive stimuli. Aprepitant modulated these brain responses during the tasks. This study has provided more insights into how the brain works at the neural level during methadone dependence and how this can be modulated by aprepitant. Future studies will explore the therapeutic potential of aprepitant further in the clinic.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
19/LO/0971
Date of REC Opinion
30 Aug 2019
REC opinion
Further Information Favourable Opinion