Addiction, Author Interviews, Opiods, PLoS / 04.02.2022 Interview with: Dr. Laurence Moss MD, PhD candidate Centre for Human Drug Research (CHDR) Department of Anesthesiology Leiden University Medical Centre (LUMC) Geert Jan GroeneveldMD, PhD Neurologist | Clinical Pharmacologist | Professor of Clinical Neuropharmacology CMO/CSO Centre for Human Drug Research Leiden, The Netherlands  What is the background for this study?    Response: Opioid use disorder (OUD) is a major source of morbidity and mortality, and the opioid epidemic in the Unites States (but increasingly in Europe also) has been well documented and reported on by the media. The alarming rise in opioid related mortality is largely driven by the increasing use of fentanyl and fentanyl analogues, often surreptitiously mixed with heroin or other drugs such as psychostimulants or prescribed opioids. Opioid-induced respiratory depression in particular is a leading cause of opioid-related fatalities. Buprenorphine has been proven as an effective medication for the treatment of OUD. Buprenorphine is a semi-synthetic partial agonist for the opioid receptor that firmly binds to these receptors and displays only partial respiratory depressive effects, meaning it does not cause the complete cessation of breathing as is the case with other potent opioids such as fentanyl. Due to its firm receptor binding, we hypothesized that at sufficient buprenorphine receptor occupancy, the effect of fentanyl on respiration would be limited, even at high fentanyl doses. This study aimed to provide proof of principle for this hypothesis, and demonstrate whether buprenorphine could reduce fentanyl-induced respiratory depression. (more…)