Nitrous Oxide and Buprenorphine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Nitrous Oxide
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Buprenorphine (found in Belbuca, Sublocade, and similar products) is an opioid, and nitrous oxide (sometimes called laughing gas, used during dental or medical procedures) is a gas that relaxes and sedates you. Both slow down your brain and your breathing. When you use them together, those effects can stack up. That can lead to heavy drowsiness, very slow or shallow breathing, and in serious cases, dangerous or even life-threatening problems.
The good news is that this is very manageable when your team knows about it. Always tell the dentist, anesthesiologist, or doctor giving you nitrous oxide that you take buprenorphine so they can watch your breathing closely and keep you safe.
Effect: Additive CNS and respiratory depression when buprenorphine (a partial mu-opioid agonist) is combined with nitrous oxide (an inhaled CNS depressant). Risk includes profound sedation, respiratory depression, coma, and death.
- Mechanism: Pharmacodynamic additive CNS depression (not a metabolic/prodrug interaction).
- Direction: Enhanced sedative and respiratory-depressant effect.
- Severity/Evidence: Major; probable.
- Management: If nitrous oxide is required, administer in a monitored setting with continuous respiratory monitoring (SpO2, capnography, sedation level). Use lowest effective doses, ensure resuscitation capability, and avoid additional CNS depressants perioperatively.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effect on the central nervous system can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using these agents concurrently, discontinuing the CNS depressant is the preferred approach. Depending on the situation, it may be suitable to observe the patient within a higher level of care or to implement a taper. For other patients, it may be appropriate to slowly withdraw a prescribed CNS depressant or to lower it to the smallest effective dose. When concurrent use cannot be avoided, exercise caution in monitoring and management, and weigh alternative therapies for treating anxiety or insomnia2. A Swedish epidemiological study found that among patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, medications used for insomnia), the risk of death was elevated. Analysis of pooled nationwide death certificate data spanning 2010 to 2014 showed that most overdose fatalities involving buprenorphine and methadone also involved concurrent use of a CNS depressant. Whether the risk of overdose death associated with concomitant CNS depressant drugs was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking your buprenorphine exactly as prescribed. Do not stop it on your own, and do not skip disclosing it before a procedure.
- Tell every provider giving you nitrous oxide (dentist, anesthesiologist, doctor) that you are on buprenorphine.
- Your care team can manage this by monitoring your breathing and sedation more closely and using the lowest effective dose of nitrous oxide.
- In some settings they may choose an alternative sedation option or provide care in a more closely monitored environment.
- Ask your pharmacist or prescriber before any planned procedure so a safe plan is in place.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) had an increased risk of death. In MAT-prescribed patients aged 18 to 50, the study examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy, over the interval from July 1, 2005 to December 31, 2012. The findings showed a raised risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with MAT plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, only the fatal overdose and all-cause mortality data reached statistical significance; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication for use of the drugs 3.
b) Based on a study of pooled nationwide death certificate data covering 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly cited as contributors to those deaths. Concomitant ALPRAZolam use was noted in 18.1% of cases, followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA documented 322 drug overdose deaths in 2014 that involved buprenorphine. Among these 322 deaths, 32.9% involved ALPRAZolam, 17.4% involved clonazePAM, 11.2% involved diazePAM, 11.2% involved heroin, and 9.9% involved fentaNYL. The absolute count of methadone-involved deaths was 10 times the count of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Nitrous Oxide and Buprenorphine together?
Buprenorphine and nitrous oxide both depress breathing and can stack dangerously, so always tell any provider giving you nitrous oxide that you take buprenorphine and let them monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nitrous Oxide and Buprenorphine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Nitrous Oxide and Buprenorphine interaction managed?
Keep taking your buprenorphine exactly as prescribed. Do not stop it on your own, and do not skip disclosing it before a procedure. Tell every provider giving you nitrous oxide (dentist, anesthesiologist, doctor) that you are on buprenorphine. Your care team can manage this by monitoring your breathing and sedation more closely and using the lowest effective dose of nitrous oxide. In some settings… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Nitrous Oxide or Buprenorphine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
Keep reading about Buprenorphine
Keep reading about Nitrous Oxide
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