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Buprenorphine

  • Prescription medicine
  • Given by a clinician
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Buprenorphine does in the body

Heroin and fentanyl turn it all the way up, which is what stops breathing at high doses.

Opioid receptors work like a dimmer switch. Buprenorphine turns it partway up and then refuses to go further, however much you take. It also grips the receptor far more tightly than other opioids, so it pushes them off and keeps them off. That is why it stops withdrawal without producing a full high, and also why taking it too soon after another opioid throws the person straight into withdrawal.

Why people take it. Used for opioid use disorder and, separately, severe long-term pain.

What happened in people

Across 31 studies, buprenorphine kept more people in treatment, while higher doses also reduced illicit opioid use.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

Starting it too soon after a potent synthetic opioid can trigger sudden severe withdrawal.

Where it acts
Mu- and kappa-opioid receptors in brainstem respiratory centres, ventral tegmental area and dorsal horn
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

What the registries record it as

  • Its recorded molecular formula is C29H41NO4, weighing 467.64.

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

A reviewer approved this sentence against this exact record and its sources.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 113 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Absolute difference

An absolute difference is how many more people in a hundred were affected.

A picture of it, and where the picture fails

It is like counting heads in two rooms of a hundred.

Where that stops being true. Heads are easy to count. Study results carry a margin of error too.

What people get wrong. It is confused with a percentage change, which can look far larger.

The arithmetic difference in event rates between arms.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Retention in treatment and suppression of illicit opioid use

The study showed what it set out to show

Who was studied
Cochrane buprenorphine maintenance (31 trials pooled)
How many people
5430
Study design
Systematic review and meta-analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Retention versus placebo RR 1.50 (low dose), 1.74 (medium), 1.82 (high); illicit use suppressed only at 16 mg or more (SMD -1.17)
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Few studies reported adverse events, which the review authors flag as a limitation of the underlying trial literature.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

All-cause and overdose mortality in and out of treatment

The study showed what it set out to show

Who was studied
Sordo mortality meta-analysis (19 cohorts pooled)
How many people
15831
Study design
Systematic review and meta-analysis of cohort studies
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Out-to-in all-cause rate ratio 2.20 (95% CI 1.34 to 3.61) for buprenorphine; 3.20 (2.65 to 3.86) for methadone
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. The authors state that confounding and selection bias are not fully accounted for and that between-drug comparisons should be treated with caution.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection

Interval reported. 95% CI 1

Written into the record, not signed off as a reviewed claim.

24-week opioid relapse events, intention to treat

The study showed what it set out to show

Who was studied
X:BOT (NCT02032433)
How many people
570
Study design
Phase 4 comparative effectiveness
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratio 1.36 (95% CI 1.10 to 1.68) favouring buprenorphine-naloxone by intention to treat; P = 0.44 per protocol
Repeated elsewhere
Unreplicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Five fatal overdoses across both arms, three in the buprenorphine group and two in the naltrexone group.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection

Interval reported. 95% CI 1

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Buprenorphine

    What a person takes: Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection.

    The measurement behind this step

    Opioid use disorder is treated with sublingual tablets or films, usually combined with naloxone as a misuse deterrent, or with a monthly extended-release subcutaneous depot. Chronic pain uses entirely different products at far lower doses: a weekly transdermal patch and a twice-daily buccal film. These are not interchangeable.

  2. Getting in

    Dissolved under the tongue, not swallowed

    The tablet or film goes under the tongue and is absorbed through the lining of the mouth, because the gut and liver would destroy almost all of it.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Sublingual administration bypasses extensive first-pass metabolism; oral bioavailability is very low. Suboxone combines buprenorphine with naloxone, which is poorly absorbed sublingually but active if the product is injected — a deterrent formulation rather than a therapeutic combination.

  3. Reaching the cell

    Reaches opioid receptors and stays there

    It grips the receptor much more tightly than heroin, morphine or fentanyl, and lets go very slowly.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Very high mu-opioid receptor affinity with slow dissociation kinetics. Metabolised by CYP3A4 to norbuprenorphine and by glucuronidation. The long receptor residence time is what allows every-other-day or thrice-weekly dosing in maintenance.

  4. What it acts on

    Turns the receptor partway on, and blocks kappa

    It activates the receptor only partially, and it blocks a second receptor associated with dysphoria.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Partial agonism at the mu-opioid receptor with submaximal intrinsic efficacy relative to a full agonist, and antagonism at the kappa-opioid receptor. The kappa antagonism is thought to contribute to mood effects and is one reason buprenorphine has been investigated in depression.

  5. The change it makes

    Respiratory depression hits a ceiling

    Taking more does not depress breathing further past a point, which is the property that makes it safe enough to prescribe outside a clinic.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Because intrinsic efficacy is submaximal, the dose-response curve for respiratory depression plateaus rather than continuing to rise as it does for full agonists. The ceiling is not absolute — it can be overwhelmed in combination with benzodiazepines, alcohol or other CNS depressants, and it does not apply to opioid-naive individuals in the same way.

  6. What that does for a person

    Withdrawal suppressed, illicit use falls, mortality falls

    Cravings and withdrawal are controlled, more people stay in treatment, and fewer of them die.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Measured endpoints are retention in treatment (RR 1.50 to 1.82 versus placebo depending on dose), suppression of illicit use on urinalysis (only at 16 mg or more), and all-cause mortality of 4.3 versus 9.5 per 1,000 person-years in versus out of treatment.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • Adults and adolescents aged 16 and older with opioid use disorder. Separate transdermal and buccal formulations are used for chronic pain at much lower doses.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What the label states about particular groups

  • On pediatric, the label states: “The safety and efficacy of buprenorphine transdermal system in patients under 18 years of age has not been established.”

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

  • On older people, the label states: “Of the total number of subjects in the clinical trials (5,415), buprenorphine transdermal system was administered to 1,377 patients aged 65 years and older.”

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

  • On people who are pregnant, the label states: “Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] .”

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

  • On people who are breastfeeding, the label states: “Risk Summary Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with buprenorphine transdermal system.”

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

  • On people with reduced liver function, the label states: “In a study utilizing intravenous buprenorphine, peak plasma levels (C max ) and exposure (AUC) of buprenorphine in patients with mild and moderate hepatic impairment did not increase as compared to those observed in subjects with normal hepatic function.”

    US prescribing information · 186e3be6-8bc0-4bb9-96f5-429d53632f45 · read 2026-08-30

Where the result stopped carrying

  • Low- and medium-dose buprenorphine did not suppress illicit opioid use on urinalysis, despite retaining patients better than placebo
  • Flexible-dose buprenorphine retained fewer patients than methadone (RR 0.83), which is a real and consistently replicated disadvantage
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Given by a clinician

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Suppression classes recorded: S1, S5, S6.

No source is stored against this line.

What is in the pack

Opioid use disorder is treated with sublingual tablets or films, usually combined with naloxone as a misuse deterrent, or with a monthly extended-release subcutaneous depot. Chronic pain uses entirely different products at far lower doses: a weekly transdermal patch and a twice-daily buccal film. These are not interchangeable.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold and what that means for what is in the pack.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Respiratory depression plateaus with dose because of partial agonism, but this ceiling can be overwhelmed by benzodiazepines, alcohol or other CNS depressants and does not protect opioid-naive individuals or children. Buprenorphine precipitates withdrawal if given while a full agonist still occupies the receptor. It is a Schedule III controlled substance in the United States. Neonatal opioid withdrawal syndrome occurs with use in pregnancy, and pregnancy is nonetheless an indication for treatment rather than a reason to stop.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Sublingual tablet and film, transdermal patch, buccal film, and extended-release subcutaneous injection

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Chronic pain uses entirely different products at far lower doses: a weekly transdermal patch and a twice-daily buccal film. These are not interchangeable.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 255 products list this as an active ingredient in the United States drug directory. 151 of them contain it and nothing else.

    FDA National Drug Code directory · 72189-580 · read 2026-08-29

  • They are sold as film, film, soluble, injection, injection, solution, patch and patch, extended release, taken buccal, intramuscular, intravenous and subcutaneous.

    FDA National Drug Code directory · 72189-580 · read 2026-08-29

  • The regulator's established pharmacologic class for it is partial opioid agonist [epc] and partial opioid agonists [moa].

    FDA National Drug Code directory · 72189-580 · read 2026-08-29

  • 106 published labels name it as an active ingredient. 51 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · 4951ec29-609b-4836-b0e4-0d9c1d6ae6fe · read 2026-08-29

  • Those labels are classed as human prescription drug.

    US prescribing information · 4951ec29-609b-4836-b0e4-0d9c1d6ae6fe · read 2026-08-29

  • Buprenorphine is sublingual tablets at Sublingual tablet: 2 mg buprenorphine and 8 mg buprenorphine, recorded as prescription product; fda label in effect 2025-02-03 in the United States.

    US prescribing information · 023c7816-21b1-4f85-be36-9e32d5935c19 · read 2026-08-27

  • Recorded price in US: 0.26477–57.31739 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 57 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..

    Recorded source · 2026-08-26 · read 2026-08-28

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.

Questions worth asking

  • Which of the trials of Buprenorphine studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That the respiratory-depression ceiling makes overdose impossible — it plateaus the curve and can still be overwhelmed with benzodiazepines, alcohol or other depressants

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That eliminating the X-waiver in 2023 would by itself expand access, when pharmacy stocking, prior authorisation and prescriber confidence remain

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That induction protocols validated in the heroin era transfer unchanged to a supply dominated by high-potency synthetic opioids

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Buprenorphine are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

High-certainty evidence for retention in treatment at every dose tested
In plain words
Across 31 trials and 5,430 people, buprenorphine kept patients in treatment better than a dummy pill at low, medium and high doses. Only the high dose reliably reduced illicit opioid use.
What was measured
Retention in treatment, relative risk versus placebo by dose band
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mattick et al. included 31 trials, 5,430 participants. High-certainty evidence that buprenorphine retained participants better than placebo at low dose 2-6 mg (RR 1.50, 95% CI 1.19 to 1.88; 5 studies, 1,131 participants), medium dose 7-15 mg (RR 1.74, 1.06 to 2.87; 4 studies, 887), and high dose 16 mg or more (RR 1.82, 1.15 to 2.90; 5 studies, 1,001). Moderate-certainty evidence that only high-dose buprenorphine suppressed illicit opioid use on urinalysis (SMD -1.17, 95% CI -1.85 to -0.49; 3 studies, 729), while low dose (SMD 0.10) and medium dose (SMD -0.08) did not. Against methadone, flexible-dose buprenorphine retained fewer patients (RR 0.83, 95% CI 0.72 to 0.95; 5 studies, 788) with no difference in suppression of use among those retained.
Source
Mattick RP et al., Cochrane Database Syst Rev 2014;2:CD002207
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
All-cause mortality more than halves while a person is in buprenorphine treatment
In plain words
Pooling cohorts covering nearly 16,000 people on buprenorphine, the death rate was 4.3 per 1,000 person-years while in treatment and 9.5 while out of it.
What was measured
All-cause and overdose mortality per 1,000 person-years, in versus out of treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sordo et al. pooled 19 cohorts: 122,885 people treated with methadone over 1.3 to 13.9 years and 15,831 treated with buprenorphine over 1.1 to 4.5 years. Pooled all-cause mortality was 4.3 per 1,000 person-years in buprenorphine treatment and 9.5 out of it (unadjusted out-to-in rate ratio 2.20, 95% CI 1.34 to 3.61); for methadone, 11.3 in and 36.1 out (rate ratio 3.20, 2.65 to 3.86). Overdose mortality was 1.4 in and 4.6 out of buprenorphine treatment. All-cause mortality dropped sharply over the first four weeks of methadone treatment but remained stable during buprenorphine induction — the induction period is the dangerous one for methadone and not for buprenorphine. The authors flag confounding and selection bias as unresolved limitations of any between-drug comparison.
Source
Sordo L et al., BMJ 2017;357:j1550
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
After a non-fatal overdose, buprenorphine was associated with 37% lower all-cause mortality
In plain words
Among people who survived an opioid overdose, those who went on to receive buprenorphine were about a third less likely to die in the following year. Only 17% of them received it.
What was measured
Adjusted hazard ratio for all-cause and opioid-related mortality
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Larochelle et al. followed opioid overdose survivors in Massachusetts. In the 12 months after a non-fatal overdose, 3,022 people (17%) received buprenorphine for a median of four months. Compared with no medication for opioid use disorder, buprenorphine was associated with decreased all-cause mortality (adjusted hazard ratio 0.63, 95% CI 0.46 to 0.87) and opioid-related mortality (0.62, 0.41 to 0.92). Methadone showed 0.47 (0.32 to 0.71) and 0.41 (0.24 to 0.70). Overall cohort all-cause mortality was 4.7 deaths per 100 person-years. The authors note that only a minority of overdose survivors received any medication at all.
Source
Larochelle MR et al., Ann Intern Med 2018;169:137-145
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
X:BOT: easier to start than naltrexone, and equal once both were started
In plain words
Nearly all patients assigned to buprenorphine were able to start it, against fewer than three quarters assigned to naltrexone. Among those who started either drug, outcomes were the same.
What was measured
Induction success rate and 24-week relapse
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Lee et al. (NCT02032433) randomised 570 patients. Induction succeeded in 270 of 287 (94%) assigned to buprenorphine-naloxone against 204 of 283 (72%) assigned to extended-release naltrexone (P<0.0001). Intention-to-treat 24-week relapse was 163 of 287 (57%) versus 185 of 283 (65%), hazard ratio 1.36 (95% CI 1.10 to 1.68) favouring buprenorphine — but in the per-protocol population of 474 successfully inducted patients, relapse events were similar (P=0.44). Opioid-negative urine samples and abstinent days favoured buprenorphine on intention to treat and were similar per protocol. Self-reported craving was initially lower on naltrexone (P=0.0012) and converged by week 24.
Source
Lee JD et al., Lancet 2018;391:309-318
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The X-waiver was eliminated in 2023, and access did not automatically follow
In plain words
For two decades, prescribing buprenorphine required a special federal waiver. That requirement was removed at the end of 2022, and the number of clinicians actually prescribing it did not jump the way the change implied it would.
What was measured
That eliminating the X-waiver would by itself substantially expand access to buprenorphine treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Consolidated Appropriations Act, 2023 eliminated the DATA 2000 waiver requirement, so any clinician with a DEA registration to prescribe controlled substances may now prescribe buprenorphine for opioid use disorder. Saloner and colleagues argued in Substance Abuse that removing the waiver addresses only one of several barriers — the others being pharmacy stocking, insurance prior authorisation, clinician confidence with induction, and stigma — and that expanded prescribing authority is a necessary but not sufficient condition for expanded access. The audit point here is the inference: a regulatory barrier being removed is not the same as a treatment gap closing.
Source
Saloner B et al., Subst Abus 2023;44:169-172
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
The classical induction protocol was built for a drug landscape that no longer exists
In plain words
The standard advice on when to take the first dose was developed when the opioids people used cleared quickly. High-potency synthetic opioids behave differently, and precipitated withdrawal has become a more common problem.
What was measured
That induction protocols and effect estimates derived from a heroin-era treatment population transfer unchanged to a population using high-potency synthetic opioids
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Buprenorphine's very high mu-receptor affinity and slow dissociation displace full agonists from the receptor while only partly activating it. The classical induction protocols specify waiting for objective withdrawal, typically assessed with a structured scale, before the first dose. Those protocols were developed and validated in a population using heroin and prescription opioids. This page records that the Cochrane evidence base for buprenorphine retention and suppression of use predates the widespread presence of high-potency synthetic opioids in the illicit supply, and that the applicability of induction timing derived from that era is an assumption rather than a finding.
Source
Mattick RP et al., Cochrane Database Syst Rev 2014;2:CD002207
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim

How many documents were read

  • 48 documents were read for this substance.

    RNAWiki source record

  • 2 of them state the same tMax, and they agree.

    RNAWiki source record

  • 7 of them state the same volumeOfDistribution, and they agree.

    RNAWiki source record

Where else this substance is registered

FDA substance identifier (UNII)
56W8MW3EN1
CAS registry number
52485-79-7
PubChem compound
644073
RxNorm concept
1819

Checks this page had to pass

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  • Passed

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    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

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    enforced by the copy-contract test over the rendered page

  • Passed

    Safety mode resolved

    Suppression classes recorded: S1, S5, S6.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

What the approval register records

  • 54 approved applications cover products containing this substance. The earliest was NDA018401, approved 19811229 to INDIVIOR.

    Drugs@FDA application register · NDA018401 · read 2026-08-29

  • Marketing status on the register: discontinued, none (tentative approval) and prescription.

    Drugs@FDA application register · NDA018401 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19960101.

    FDA National Drug Code directory · 72189-580 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

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What is not here

7 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

  • What was measured, goal by goal — found nothing in the sources checked.
  • How close this is to real life — found nothing in the sources checked.
  • Felt, measured, or meaningful — found nothing in the sources checked.
  • How long anything takes — found nothing in the sources checked.
  • What it may clash with — found nothing in the sources checked.
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The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

A tightly binding partial opioid agonist that keeps people in treatment better than placebo at every dose tested, and is associated with roughly a halving of all-cause mortality in the year after an overdose — with a ceiling on respiratory depression that is its defining safety property and a precipitated-withdrawal risk that is its defining practical problem.

Recorded evidence blocks (8)

On the Buprenorphine label: indicated for what?


"SUBLOCADE is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. SUBLOCADE should be used as part of a complete treatment plan that includes…": indications and usage on Buprenorphine's label. DailyMed label · 6189fb21-9432-45f8-8481-0bfaf3ccde95 · 2026-07-27

305 registered trials of Buprenorphine — at which phases?


Registered studies posting no result
185 of 305

305 registered studies of Buprenorphine: 99 phase2, 74 phase3, 73 phase4, 51 phase1, 15 na, 15 na or unstated, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01

1452 with a PubMed record

Show the evidence
  • phase2
    99
  • phase3
    74
  • phase4
    73
  • phase1
    51
  • na
    15
  • na or unstated
    15
10 more recorded rows
  • early phase1
    3
  • completed
    214
  • terminated
    29
  • recruiting
    19
  • unknown
    16
  • withdrawn
    16
  • not yet recruiting
    7
  • active not recruiting
    2
  • enrolling by invitation
    1
  • suspended
    1

recorded 2026-09-01 · last checked 2026-09-04

45 of Buprenorphine's trials stopped: safety, accrual/recruitment, funding/business, sponsor decision unspecified, other?


safety (7), accrual/recruitment (8), funding/business (9), sponsor decision unspecified (4) and other (17): Buprenorphine's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01

"The trial was terminated because of deviations from the protocol."; 45 of 305 registered studies

Show the evidence

Trial

  • NCT00279565
    terminated; "The trial was terminated because of deviations from the protocol."
  • NCT00312221
    terminated; "terminated early for administrative reasons unrelated to safety or efficacy"
  • NCT00313014
    terminated; "Terminated early due to administrative reasons unrelated to efficacy or safety."
  • NCT00315458
    terminated; "Administrative reasons."
  • NCT00320801
    terminated; "This study was terminated early due to administrative reasons."
  • NCT00403234
    terminated; "due to administrative reasons not related to efficacy or safety."
14 further recorded trials
  • NCT00469053
    terminated; "The trail end was achived according to the definition in the trial protocol"
  • NCT00469404
    terminated; "The trial end was achieved according to the definition in the trial protocol"
  • NCT00552578
    terminated; ""Tapering doses" protocol arm was not effective for treatment retention outcome."
  • NCT00916890
    suspended; "difficulties in patients enrolment"
  • NCT00947466
    terminated; "25 patients have been recruited and it was considered that further recruitment would add no extra PK information"
  • NCT00949299
    terminated; "Not enough could be recruted"
  • NCT01015066
    withdrawn; "Study personnel left institution, anticipated funding did not occur"
  • NCT01125917
    terminated; "Terminated early due to administrative reasons."
  • NCT01135524
    terminated; "This study was terminated early for administrative reasons."
  • NCT01324544
    withdrawn; "Due to change in development plan."
  • NCT01583179
    terminated; "The study was closed prematurely due to low enrollment and anticipation of future barriers in enrollment"
  • NCT01841931
    terminated; "Principal Investigator is no longer at this site"
  • NCT01875848
    terminated; "Data safety monitoring board recommended due to low recruitment yield."
  • NCT02138357
    withdrawn; "No funding"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Buprenorphine used Buprenorphine 5mg, 10mg, 20mg vs Tramadol 100mg — over how long?


studies of Buprenorphine used the recorded amount. ClinicalTrials.gov · 2026-09-01

13 recorded entries; human; sublingual, injection; also "Buprenorphine 5mg, 10mg, 20mg vs Tramadol 100mg", "2.0mg Buprenorphine/0.5mg Naloxone", "Buprenorphine 0.2 MG Sublingual Tablet"

Show the evidence

human

  • NCT01019265
    Buprenorphine 5mg, 10mg, 20mg vs Tramadol 100mg
  • NCT01846455
    2.0mg Buprenorphine/0.5mg Naloxone
  • NCT01860287
    Buprenorphine 0.2 MG Sublingual Tablet
  • NCT01860287
    Buprenorphine 0.4 MG Sublingual Tablet
  • NCT02162121
    Buprenorphine 0,2mg
  • NCT02659787
    0.2mg Buprenorphine
7 more recorded rows
  • human NCT03996694
    Belbuca 300 µg
  • human NCT03996694
    Belbuca 600 µg
  • human NCT03996694
    Belbuca 900 µg
  • human NCT04254081
    Buprenorphine 0.15 MG
  • human NCT05549492
    buprenorphine 300 μg
  • human NCT07439549
    sublingual; Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg)
  • human NCT07439549
    injection; Buprenorphine extended-release injection (300 mg/1.5 mL)

recorded 2026-09-01 · last checked 2026-09-04

Buprenorphine's half-life is 43 to 60 days — which schedules were studied?


43 to 60 days, the half-life Buprenorphine's label states: "The apparent terminal plasma half-life of buprenorphine following subcutaneous injection of SUBLOCADE ranged between 43 to 60 days as a result of the slow release of buprenorphine from the subcutaneous depot." DailyMed label · 6189fb21-9432-45f8-8481-0bfaf3ccde95 · 2026-07-27

tmax 24 hours.

Show the evidence
  • half life pharmacokinetics
    43 to 60 days; The apparent terminal plasma half-life of buprenorphine following subcutaneous injection of SUBLOCADE ranged between 43 to 60 days as a result of the slow release of buprenorphine from the subcutaneous depot.
  • tmax pharmacokinetics
    24 hours; After SUBLOCADE injection, an initial buprenorphine peak was observed and the median T max occurred at 24 hours after injection.
  • metabolism pharmacokinetics
    Elimination Buprenorphine is metabolized and eliminated in urine and feces.

recorded 2026-07-27 · last checked 2026-09-04

Which 79 trials of Buprenorphine posted no result?


Posted no result
79 of 79 completed trials
Registrations
NCT00000214, NCT00000205, NCT00000357, NCT00000210, NCT00000211 and NCT00000355, and 73 more
Completion dates
oldest 1993-01; newest 2023-03-30
Show the evidence

Trial

  • NCT00000214
    1993-01
  • NCT00000205
    1993-09
  • NCT00000357
    1993-10
  • NCT00000210
    1996-02
  • NCT00000211
    1996-02
  • NCT00000355
    1996-03
14 further recorded trials
  • NCT00158236
    1998-03
  • NCT00134914
    1998-05
  • NCT00015041
    1998-07
  • NCT00000311
    1999-02
  • NCT00000320
    1999-08
  • NCT00000341
    2000-08
  • NCT00000219
    2001-07
  • NCT00000220
    2001-07
  • NCT00007527
    2002-01
  • NCT00367874
    2003-11
  • NCT00023283
    2004-02
  • NCT00000216
    2005-01
  • NCT00000319
    2005-01
  • NCT00000334
    2005-01-15

At the median, Buprenorphine's trials enrolled 46 people — anything larger?


Median enrolment
46
Largest enrolment
3000
Registered trials counted
304

Buprenorphine and CYP3A4: shared by which compounds?


CYP3A4 appear in Buprenorphine's recorded interaction sentences, 8 in all. DailyMed label · 6189fb21-9432-45f8-8481-0bfaf3ccde95 · 2026-07-27

CYP3A4, CYP3A4; 2 shared nodes; drug_interactions

Show the evidence

Interaction statement

  • drug_interactions
    Inhibitors of CYP3A4 Clinical Impact: The effects of co-administered CYP3A4 inhibitors on buprenorphine exposure in subjects treated with SUBLOCADE have not been studied and the effects may be dependent on the route of administration; however, such interactions have been established in studies using transmucosal buprenorphine.
  • drug_interactions
    Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when SUBLOCADE is given concurrently with agents that affect CYP3A4 activity.
  • drug_interactions
    The concomitant use of sublingual buprenorphine and CYP3A4 inhibitors (e.g., ketoconazole) can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects.
  • drug_interactions
    Intervention: Patients who transfer to SUBLOCADE treatment from a regimen of transmucosal buprenorphine used concomitantly with CYP3A4 inhibitors [e.g., azole antifungals such as ketoconazole, macrolide antibiotics such as erythromycin, and HIV protease inhibitors (e.g., ritonavir, indinavir, and saquinavir)] should be monitored to ensure that the plasma buprenorphine level provided by SUBLOCADE…
  • drug_interactions
    If patients already on SUBLOCADE require newly-initiated treatment with CYP3A4 inhibitors, the patients should be monitored for signs and symptoms of over-medication.
  • drug_interactions
    Conversely, if a patient has been stabilized on SUBLOCADE in the setting of concomitant medication that is a CYP3A4 inhibitor, and the concomitant medication is discontinued, the patient should be monitored for withdrawal.
2 more recorded rows
  • Interaction statement drug_interactions
    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The effects of co-administered CYP3A4 inducers on buprenorphine exposure in subjects treated with SUBLOCADE have not been studied.
  • Interaction statement drug_interactions
    Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when SUBLOCADE is given concurrently with agents that affect CYP3A4 activity.

CYP3A4

  • FINGOLIMOD LAURYL SULFATE, ERYTHROMYCIN LACTOBIONATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Beclometasone, Rasagiline, Sofpironium
  • FINGOLIMOD LAURYL SULFATE, ERYTHROMYCIN LACTOBIONATE, FOSAPREPITANT DIMEGLUMINE, TAFAMIDIS MEGLUMINE, Arimoclomol, Beclometasone, Rasagiline, Sofpironium

recorded 2026-07-27 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

PubChem CID
644073
CAS number
52485-79-7
RxCUI
1819
InChIKey
RMRJXGBAOAMLHD-IHFGGWKQSA-N
Salt form
Buprenorphine Hydrochloride, Buprenorphine HCl
Trade name
Brixadi, Belbuca, Butrans, Buprenorphine Transdermal System, Sublocade, Buprenorphine Sublingual, Buprenorphine Sublingual C-III, Subutex / Suboxone / Butrans / Belbuca / Sublocade, Anorfin, Bunavail component buprenorphine hydrochloride, Buprenex, Zubsolv
Also called
Buprederm, Buprenorphine hydrochloride CIII, Buprenorphine hydrochloride [EP IMPURITY], Buprenorphine hydrochloride [EP MONOGRAPH], Buprenorphine hydrochloride [JAN], Buprenorphine hydrochloride [MART.]
Sources (6)

Sources

  • CLINICALTRIALS_SNAPSHOT K1:40D3SCR4GZ ·
  • ClinicalTrials.gov clinicaltrials.gov ·
  • drugsfda+ema drugsfda+ema ·
  • DailyMed label 186e3be6-8bc0-4bb9-96f5-429d53632f45 ·
  • DailyMed label 6189fb21-9432-45f8-8481-0bfaf3ccde95 ·
  • Drugs@FDA K1:40D3SCR4GZ ·

ClinicalTrials.gov — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 6 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
  • no raw internal fields: enforced by the copy-contract test over the rendered page

This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.