Could you tell us a little bit about who you are, where you work and what you are currently working on?

I am Leandro Vendruscolo. I am a staff scientist at the National Institute on Drug Abuse in the United States, which is part of the National Institutes of Health and I have been working on the neurobiology of stress and addiction for about 20 years, mainly using preclinical models.

Could you tell us a little bit more about your key part and why you think this topic is so important?

I think opioid use disorders are very important because we know that opioid overdose fatalities in the United States and in other countries have risen substantially in the last few years and opioid overdose deaths, such as those caused by heroin, and fentanyl, are now considered a public emergency. We know that one of the major contributors to the opioid crisis is opioid use disorder. We have been conducting our research, trying to understand the neurobiological mechanisms that underlie opioid use disorder. In our paper, what we did was investigate opioid dependence. We know that opioids are rewarding drugs, which means that they cause pleasure.

However, from a stress standpoint, as opioid addiction develops, opioid withdrawal becomes very intense, and opioid withdrawal is severely dysphoric, it's not pleasant and it's emotionally painful. We also believe that these negative emotional states can contribute to drug-taking, drug-seeking, and drug relapse. Our hypothesis was that opioid dependence engaged the activation of specific stress-associated brain systems. To understand that, we use our models of opioid addiction, and we identified a particular stress system called the glucocorticoid receptor. We found that this system is sensitized in opioid dependence, and it also is functionally involved in opioid taking and seeking.

From this article, we identified the glucocorticoid receptors as a viable therapeutic target for the treatment of the stress component of opioid use disorder.

What's the connection between your research and medical practice? How do you hope your work will have an impact on therapies, treatments, and patient outcomes in the future?

This study that we did is an initial step towards the goal of finding better treatment for people with opioid use disorder and contributing to the reduction of opioid-related deaths. I believe that studying opioid use disorder from a stress standpoint, will lead to the discovery of novel biological systems with the potential for alleviating opioid withdrawal, and consequently, decreasing opioid intake, seeking and preventing relapse.

Where do you think your work will lead you to next what is your dream outcome or ultimate aim?

Glucocorticoid receptor antagonists are already approved for the treatment of people with Cushing's Syndrome, which is characterized by the overactivity of hypothalamic-pituitary-adrenal axis and glucocorticoid receptor systems. There is a drug already used in people, we know that this drug is safe and tolerable. We also know that the same medication has been tested for alcohol use disorder with positive results, which we published a few years ago. We know that that medication may be of potential use in substance use disorder. I think that this medication already available for clinical practice could be repurposed for the treatment of people with opioid use disorder.