Trial reportPloS one2022
Effect of sustained high buprenorphine plasma concentrations on fentanyl-induced respiratory depression: A placebo-controlled crossover study in healthy volunteers and opioid-tolerant patients.
Trial report in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03747341 (A Study Examining the Pharmacodynamics Interaction Between Buprenorphine and Fentanyl), which is not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Study Examining the Pharmacodynamics Interaction Between Buprenorphine and Fentanyl
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Evidence-based consensus guidelines for the pharmacological management of substance dependence: Recommendations from the British Association for Psychopharmacology.Journal of psychopharmacology (Oxford, England) · 2026Guideline
- The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.Drug design, development and therapy · 2023Trial
- Trial
- Opioids to Treat Chronic Pain in the Older Adult: A Clinical Consensus to Guarantee Safety and Avoid Adverse Events.Drugs & aging · 2026Review
- Can Buprenorphine Be Overdosed? The Ceiling Effect and Its Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Reframing Buprenorphine as a Pharmacologic Modifier of Opioid-Induced Respiratory Depression in the Fentanyl Era.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Risk of opioid overdose during buprenorphine treatment for opioid use disorder in the fentanyl era.Addictive behaviors · 2026Article
- Potentiation of fentanyl-induced respiratory depression by alcohol is not fully reversed by naloxone.JCI insight · 2026Article
- Perioperative Management of Patients on Buprenorphine.Current pain and headache reports · 2026Review
- Expanding Horizons of Buprenorphine: A Comprehensive Narrative Review of Its Pharmacological Properties and Clinical Applications in Chronic Pain.Pain and therapy · 2025Review
- Initiation and Dosing of Extended-Release Buprenorphine: A Narrative Review of Emerging Approaches for Patients Who Use Fentanyl.Substance abuse and rehabilitation · 2025Review
- Article
- Methadone and Buprenorphine in the Perioperative Setting: A Review of the Literature.Current pain and headache reports · 2024Review
- Respiratory Depression Associated with Opioids: A Narrative Review.Current treatment options in oncology · 2024Review
- Buprenorphine, oxycodone, hydrocodone, and methadone mortality in the United States (2010‒2017).Journal of the American College of Emergency Physicians open · 2024Article
- Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Quantifying a potential protective effect of buprenorphine on fatality risk during acute fentanyl exposures.Journal of substance use and addiction treatment · 2024Article
- Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.Nature communications · 2023Article
- The impact of opioids on the transcriptional landscape of human villous trophoblasts.Placenta · 2023Article
- Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.Drug and alcohol dependence reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOpioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentrations similar to those achieved with some extended-release injections used to treat opioid use disorder could reduce the frequency and magnitude of fentanyl-induced respiratory depression.
methodsIn this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded.
resultsFentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13-40%) and 47% (37-59%) compared to 51% (38-64%) and 79% (69-89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21-76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68-132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001).
interpretationResults from this proof-of-principle study provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids like fentanyl.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.