Heroin, drugs CDC/ Louis Alexander

Study Finds Buprenorphine Can Reduce Harmful Effects of Fentanyl on Respiration

MedicalResearch.com 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
Centre for Human Drug Research
Leiden, The Netherlands 

MedicalResearch.com:  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.
MedicalResearch.com:  What are the main findings?

Response: The main finding of the study was that the hypothesis was confirmed: buprenorphine can reduce the harmful effects of fentanyl on respiration and limit fentanyl-induced respiratory depression. This was especially evident in the chronic opioid users group, which included patients receiving care for OUD. High sustained buprenorphine plasma concentrations of 2 and 5 ng/mL, similar to those achieved with some extended-release injections used to treat OUD, were effective in reducing the frequency and magnitude of respiratory depression at fentanyl doses that caused clinically 

MedicalResearch.com: What should readers take away from your report?

Response: These results provide the first evidence that at relevant systemic exposures, buprenorphine can reduce respiratory depression induced by fentanyl. This knowledge may have implications for physicians treating patients with OUD when making decisions regarding the therapy. I would recommend them to read the results and look at the example graphs. When I teach pharmacology classes, I now use the beautiful results of this study as a textbook example of the interaction of partial and full agonists.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Future research in clinical practice designed to confirm the effect of buprenorphine against this fatal consequence of opioid misuse is warranted. Additionally, given that this study focused primarily on the ventilatory response, effects of buprenorphine on fentanyl-induced analgesia remain to be explored. Those results might impact treatment decisions that are made, for example, when patients on buprenorphine present at the ER and require strong analgesic therapy.

MedicalResearch.com: Is there anything else you would like to add?

Response: This study could be performed thanks to the excellent collaboration between the anesthesiology department of the Leiden University Medical Centre (LUMC) and the Centre for Human Drug Research (CHDR), both located in the Leiden bioscience park in The Netherlands. My explicit gratitude goes out to the participants in our study, and the addiction clinics that enabled the inclusion of this delicate patient group. We hope that our research contributes to the continuous improvements in the field of addiction medicine. This study was supported by Indivior Inc. The funder of the study and affiliated authors participated in designing the study, data analysis, and interpretation of the data.


Effect of sustained high buprenorphine plasma concentrations on fentanyl-induced respiratory depression: A placebo-controlled crossover study in healthy volunteers and opioid-tolerant patients
January 2022 PLoS ONE 17(1):e0256752

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Last Updated on February 4, 2022 by Marie Benz MD FAAD