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28 June 2023

Using a multidisciplinary approach to characterise the neurobiology of addiction

We caught up with Lexi Hayes from Imperial College London, who spoke to us about how CANTAB™ helped them to characterise the neurobiology of addiction in opioid dependence.

My name is Lexi Hayes and I am a final year MRC-DTP PhD candidate working in the addictions team at Imperial College London. I am specifically interested in the role of impulsivity in substance use and dependence. For the past four years, I have been working on the collection and analysis of data from the NCORE study.

Our research group uses a multidisciplinary approach to characterise the neurobiology of addiction. We aim to identify biomarkers of addiction through combining neuroimaging, pharmacology and cognitive neuroscience. This is used to predict clinical features and relapse and treatment efficacy to facilitate the development of novel treatments.

What are you investigating?

Opioid addiction is a major health challenge with death rates at an all-time high. In 2018 England and Wales had the highest annual increase (16%) in drug-related deaths since records began and over half of these deaths (51%) involved an opioid [1].
A key challenge in treating opioid addiction is preventing relapse once a person is abstinent. Opioid substitution therapies (OST) such as methadone and buprenorphine are commonly used therapeutically, alongside psychosocial therapy, to try and prevent relapse and minimise harm to the individual.

Chronic opioid exposure is associated with a range of physiological symptoms including impaired respiratory function, cardiovascular disorders and severe and lethal sleep disorders. We also see impaired cognitive function including reduced performance in inhibitory control, verbal working memory, decision making and emotional and reward processing . As a result, there is now a drive to achieve abstinence. However, abstinence can be difficult to achieve due to the range of withdrawal effects associated with cessation of opioids. These include but are not limited to muscle aches, sweating, sleep disturbances and craving. These symptoms often perpetuate drug use and can lead to relapse.

We have previously shown that Aprepitant, an NK1 receptor antagonist, ameliorates impairments in fronto-striatal network response during reward, inhibitory control and emotional processing in abstinent drug and alcohol dependent participants. In our current study, Neural Correlates of Reward and Emotion in Opioid Dependence (NCORE) we aimed to identify brain processes of reward and emotional processing in opiate dependence, during methadone maintenance. We also sought to investigate the modulation of these processes by NK1 antagonism and evaluate its potential as a therapeutic target to facilitate opiate detoxification and/or improve relapse prevention in early abstinence.

What methods did you use?

We used a double-blind randomised, placebo-controlled cross-over study of a single dose of aprepitant in opiate-dependent participants who were taking methadone and healthy controls. Participants attended a baseline session during which they completed a range of neurocognitive assessments including a battery of CANTAB tasks. Following this session, participants then attended a further two experimental sessions. In these sessions they received a single dose of placebo or aprepitant in a randomised cross-over design and completed three tasks during fMRI; cue-reactivity, monetary incentive delay and an evocative images tasks.

Which CANTAB tasks did you use?

To assess cognitive function in opioid dependence we chose CANTAB tasks that measure cognitive functions that we know are characteristically impaired following chronic opioid exposure. These included; Rapid Visual Information Processing (RVP), Cambridge Gambling Task (CGT), Intra-Extra Dimensional Set Shift (IED), Spatial Working Memory (SWM), Stop Signal Task (SST), Emotional Bias Task (EBT), Multi-Tasking Test (MTT).

What we will use CANTAB for in our study

Previous studies have demonstrated impaired neurocognitive functioning in people with opioid use disorder. Recent evidence has also suggested ‘hot’ and ‘cold’ cognitive processes may be divergently affected in recreational vs treatment-seeking drug users [2]. ‘Hot’ cognitive processes require emotional and motivational regulation, whereas ‘cold’ cognitive processes are independent of emotion. We plan to investigate whether methadone-maintained opioid-dependent participants demonstrate differences in neurocognitive function compared with healthy volunteers, specifically examining differences in ‘hot’ and ‘cold’ cognitive tasks from the CANTAB battery. We hypothesise that the opioid-dependent group will demonstrate cognitive impairments in both ‘hot’ and ‘cold’ cognitive tasks compared with healthy volunteers.

Why did we choose CANTAB?

We chose CANTAB as it is automated, standardised and user-friendly. It provides clear instructions and practice trials to allow for collection of accurate neurocognitive data. It also has a wealth of normative data that enables comparison of outcomes. The support we have received from Cambridge Cognition has been unparalleled, especially during COVID-19 when we had to make some amendments to our study protocol.

References 

[1] Office for National Statistics (2019) Deaths Related to Drug Poisoning inEngland and Wales 2018 Registrations (Statistical Bulletin). ONS.)

[2] Savulich G, Bowden-Jones O, Stephenson R, Brühl AB, Ersche KD, Robbins TW, Sahakian BJ. “Hot” and “Cold” cognition in users of club drugs/novel psychoactive substances. Frontiers in psychiatry. 2021:333.

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Author:

Alexandra Hayes

Medical Research Council Doctoral Training Partnership (MRC DTP) PhD Candidate, Imperial College London

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