Improving outcomes in heroin addiction: characterising neural and behavioural correlates of reward and emotion in people treated with buprenorphine

Opioid dependence (OpD) is a major global health challenge, with opioid-related deaths consistently breaking record levels. Increasing opioid availability and purity of synthetic products (i.e. fentanyl, nitazenes), as well as co-use of stimulants (e.g. cocaine, amphetamines), are emerging threats to managing this evolving crisis. Individuals with OpD (iOpD) generally have other physical and mental health problems that mutually exacerbate each other, requiring comprehensive care across services. In the UK, societal costs of illicit drug use (i.e. policing, crime, health and social care) reached £20 billion per annum, of which heroin and/or cocaine use contributed 86%. To develop improved OpD treatments considering these growing challenges, we urgently need a better understanding of how established therapies work. Opioid agonist therapy (OAT), also known as substitution, principally with methadone and buprenorphine (World Health Organisation essential medicines), is the mainstay treatment for OpD. Total abstinence has many health advantages. However, less than a quarter of iOpD leave treatment opioid-free, and up to 90% of those discontinuing OAT relapse within a month. Ultimately, the most suitable approach is the one that best maintains patients’ wellbeing. Currently, insufficient evidence exists to guide OAT prescribing, and surprisingly, little is known about buprenorphine’s mechanism of action in the brain. The cyclical relapsing-remitting nature of addiction is linked to disruptions in the brain’s reward system and its ability to process emotions and execute cognitive functions (e.g. attention, memory, impulsivity). These aberrations contribute to craving, which trigger relapse: opioid use ‘on-top’ of OAT or after achieving abstinence. Buprenorphine is pharmacologically distinct from methadone, and differences in the subjective experience on these drugs has been reported. Despite buprenorphine’s advantageous safety profile, which prevents overdose and attenuates emotional dysregulation, it only represents 10-30% of OAT prescribed. Meanwhile, the rollout of long-acting injectable buprenorphine formulations is paving the way for increased, sustained use. I aim to improve the understanding of brain changes in OpD relapse and buprenorphine’s mechanism of action through neuroimaging, cognitive, physiological and self-reported data from buprenorphine-maintained iOpD. In long-term abstinent people with OpD, the Imperial College Addiction Research Group demonstrated blunted responses in brain regions mediating reward and heighted responses to negative images in an area involved in emotional processing. Similar blunting of reward and greater responses to drug-related cues were also found in methadone-maintained individuals. I will test the hypotheses that buprenorphine-maintained iOpD will show the same responses as methadone-maintained iOpD compared to healthy controls (people without OpD). Researching how buprenorphine attenuates processes underpinning craving and relapse will illuminate its effectiveness in managing OpD. My findings will enrich the OAT evidence base, allowing patients and prescribers to make more informed treatment decisions. A better understanding of OpD and buprenorphine’s impact on the brain will help reveal where to target new treatments, including medications, brain stimulation techniques and psychological (talking) therapies. This research focus will strengthen methods evaluating addiction, including neuroimaging biomarkers, which can be used to predict treatment responses and outcomes. Accompanied neuroimaging data collection with monitors measuring eye movement, pupil size, and heart rate could contribute to the development of more affordable, scalable, biological investigations assessing craving. Additionally, objectively evaluating addiction helps address the stigma experienced by iOpD and their families, improving quality of life and access to care. Overall, these advances will contribute to reduced risk of relapse, overdose, and death and, in turn, ameliorate societal costs.