Ketamine 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
Ketamine
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.
Both buprenorphine and ketamine can slow down your brain and your breathing. When you take them together, those effects can add up. That can make you very sleepy, and in serious cases it can slow your breathing down too much, which can be dangerous.
This does not mean you can't use both if your care team decides you need them. It just means they will want to watch you more closely and use the lowest doses that work. Please don't start, stop, or change either medicine on your own. Talk with your pharmacist or doctor, and get help right away if you feel very drowsy, confused, or short of breath.
Effect: Additive CNS and respiratory depression with combined buprenorphine plus ketamine.
Mechanism: Pharmacodynamic additive CNS depression (not a prodrug or enzyme-based interaction). Buprenorphine is a partial mu-opioid agonist; ketamine adds dissociative sedation and its own respiratory depressant potential, especially at higher/parenteral doses.
- Direction/magnitude: Increased risk of profound sedation, respiratory depression, coma, death.
- Onset: Unspecified; effect tracks dosing/exposure.
- Evidence: Probable; major severity.
- Management: Use lowest effective doses; monitor respiratory status and sedation, consider higher level of care for parenteral ketamine. Do not withhold MAT solely due to this interaction.
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. Discontinuing the CNS depressant is preferable to using the two drugs at the same time. Depending on the situation, it may be suitable to observe the patient in a setting offering a higher level of care, or to implement a taper. In other circumstances, the appropriate approach may be to slowly wean the patient off a prescribed CNS depressant or to reduce the dose to the lowest amount that remains effective. Should concurrent use prove unavoidable, exercise caution in monitoring and managing the patient, and think about turning to alternative treatments for anxiety or insomnia2. 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 instance, agents used to treat insomnia) faced a higher risk of death. Data drawn from aggregated nationwide death certificates spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved the concurrent use of a CNS depressant. Whether buprenorphine and methadone differ in the risk of overdose death when combined with CNS depressant drugs remains unknown3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The goal is to use both safely, not to stop your treatment. Your care team can manage this combination by tailoring your doses and watching you more closely.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest effective doses and may monitor you more closely, sometimes in a higher level of care when ketamine is given.
- Tell your pharmacist about any other sedating medicines, sleep aids, anxiety meds, or alcohol.
- Ask your prescriber or pharmacist before making any changes, and seek help right away for heavy drowsiness, confusion, or slow or shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) An epidemiological investigation conducted in Sweden found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used for insomnia) have a heightened risk of death. From July 1, 2005 through December 31, 2012, researchers examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed against periods without such therapy in MAT patients (aged 18 to 50). 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 combined MAT and benzodiazepine treatment; however, these data were not regarded as statistically significant. Although the results indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were given together, 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. The authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication for which the drugs were used 3.
b) Based on a review of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often identified as contributors to those deaths. Concurrent ALPRAZolam use appeared 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 that of buprenorphine-involved deaths, though confounding factors and variations in drug utilization were not taken into account. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Ketamine and Buprenorphine together?
Buprenorphine and ketamine both depress the brain and breathing, so together they raise the risk of heavy sedation and slowed breathing; keep taking both as prescribed and let your care team monitor you closely and use the lowest effective doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketamine 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 Ketamine and Buprenorphine interaction managed?
The goal is to use both safely, not to stop your treatment. Your care team can manage this combination by tailoring your doses and watching you more closely. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may use the lowest effective doses and may monitor you more closely, sometimes in a higher level of care when ketamine is given. Tell your pharmacist… 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 Ketamine 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 Ketamine
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