Characterising the effects of chronic opioid use on regulatory control and the development of compulsivity in heroin addiction.

• Applicant: Professorin Dr. Karen Ersche
• Subject Area: Biological Psychiatry
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428016789

Drug addiction is a major public health problem that causes significant harm. Opiates are one of the most addictive drugs on the market and the increasing use of prescription opioids contributed to the stark rise in the rates of opiate addiction worldwide. Although in Europe the numbers of people addicted to opiates have been relatively stable, the expanding drug markets and the increasing availability of synthetic opioids over the internet are a growing concern, rendering treatments of opiate addiction more pressing than ever before. Yet, there are no theoretically principled treatment strategies, which target the neurobiological mechanisms underlying the development of opioid addiction. The mainstay of current treatment is still substitution therapy, i.e. replacing short-acting opiates like heroin with longer-acting opioids like methadone. Substitution therapy only has limited efficacy in achieving long-term abstinence because addicted individuals tend to top up their substitution prescription will illicit opioids. Critically, substitution therapy does not treat the maladaptive behaviours of addicted individuals; on the contrary, the behaviour persists despite negative consequences for the users’ health. Animal studies suggest that chronic use of opiates disrupts brain systems implicated in the regulation of behaviour, thus rendering behaviour inflexible and impairing patients’ ability to appreciate the consequences of their actions. However, these findings largely derive from studies of dopaminergic stimulant drugs, whilst the effects of opioids on behavioural control are still poorly understood. Here we propose a study to examine the changes in regulatory control systems associated with chronic opiate use to identify the mechanisms underlying the compulsive use of opioids. We will examine three groups of individuals: one group who is prescribed opioids as a substitution treatment for opiate addiction, another one with prescribed opioids for chronic pain (non-addicted), and one of healthy individuals who have no prior experience with opioids. The primary goal of the study is to evaluate the effects of regular opioid use on habit formation and goal-directed learning using selective neurocognitive tasks, which have been developed based on animal models. The secondary goal is to use neuroimaging technology to investigate the neural network of functionally interacting cortical and subcortical regions (both when challenged and at rest) to provide information on brain systems underpinning abnormal habit formation. These insights will yield important scientific advances for drug addiction research and will be crucial for the development of therapeutic and/or preventative interventions designed to target individuals’ resistance to behaviour change despite negative consequences. It will also provide proof-of-concept to support future studies investigating markers of risk and resilience in opioid addiction, which we are planning to succeed this study.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Christian Büchel