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Diamorphine

  • Prescription medicine
  • Not available
  • 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 Diamorphine does in the body

Severe pain in the United Kingdom, or supervised treatment for otherwise resistant opioid dependence.

Heroin is not itself an opioid painkiller. It is morphine with two greasy handles bolted on, which let it cross from blood into brain several times faster than morphine can. Enzymes in the blood and brain then snap those handles off, and what is left binding the receptor is morphine — the same drug, arriving faster. That speed is the entire difference: the receptor, the analgesia, the constipation and the respiratory depression are morphine's, and the rush is the rate of arrival.

What happened in people

Supervised medical heroin stopped street-heroin use in 72 in 100 long-term users versus 27 with optimised methadone.

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

Today’s illicit North American supply often contains fentanyl, nitazenes or xylazine instead, making older heroin risk estimates misleading.

Where it acts
Mu-opioid receptors in the periaqueductal grey, spinal dorsal horn, ventral tegmental area and the pre-Bötzinger complex of the brainstem
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · 70D95007SX · read 2026-08-29

  • Its recorded molecular formula is C21H23NO5, weighing 369.4.

    PubChem record · 5462328 · read 2026-08-29

Where each sentence above came from

No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

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

The four opening statements run to 114 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.

Stand-in result

A stand-in result is a number measured because the real result takes too long.

A picture of it, and where the picture fails

It is like judging a journey by the speedometer rather than by arriving.

Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.

What people get wrong. A stand-in result is often reported as the result itself.

A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

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.

50% or more street-heroin-negative weekly urine specimens during weeks 14 to 26

The study showed what it set out to show

Who was studied
RIOTT (ISRCTN01338071)
How many people
127
Study design
Multisite open-label randomised controlled trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Injectable heroin 72% vs oral methadone 27%, OR 7.42 (95% CI 2.69 to 20.46), p<0.0001; NNT 2.17
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. Injectable methadone did not separate significantly from oral methadone (OR 1.74, p=0.264), so the effect is specific to heroin rather than to the injectable route or the supervised clinic.

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

Form and route. Injection — intravenous, intramuscular or subcutaneous; freeze-dried powder for reconstitution

Interval reported. 95% CI 2

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

Retention in addiction treatment or drug-free status at 12 months, and reduction in illicit-drug use or other illegal activity

The study showed what it set out to show

Who was studied
NAOMI (NCT00175357)
How many people
226
Study design
Phase 3 open-label randomised controlled trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Retention 87.8% vs 54.1% (rate ratio 1.62, 95% CI 1.35 to 1.95, P<0.001); illicit-activity reduction 67.0% vs 47.7% (rate ratio 1.40, 1.11 to 1.77, P=0.004)
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. Overdoses in 10 patients and seizures in 6 in the diacetylmorphine arm, all in a supervised setting with medical staff present — which is why the authors made supervision a condition of the conclusion.

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

Form and route. Injection — intravenous, intramuscular or subcutaneous; freeze-dried powder for reconstitution

Interval reported. 95% CI 1

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

What we know
RNAWiki holds 2 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 happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event No evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life No evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.3 registered measures of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals No evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
  8. Cells in a dish No evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

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

    Diamorphine

    What a person takes: Injection — intravenous, intramuscular or subcutaneous; freeze-dried powder for reconstitution.

    The measurement behind this step

    The UK medicine is a sterile freeze-dried powder reconstituted before use. Its high solubility means a large opioid dose fits in a small volume, which is the practical reason palliative-care services use it in subcutaneous syringe drivers where morphine salts would need several times the fluid. In heroin-assisted treatment the injection is given in a licensed clinic, witnessed, with medical staff and resuscitation equipment present — a requirement that came directly out of the overdose and seizure events recorded in the trials.

  2. Getting in

    Injected, smoked or insufflated; medically, injected

    The UK medicine is a powder dissolved and injected into a vein, a muscle or under the skin. It dissolves in far less water than morphine, which is why it suits slow infusion pumps.

    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

    Diamorphine hydrochloride is supplied as a freeze-dried powder for reconstitution and given intramuscularly, intravenously or subcutaneously; glucose infusion is the preferred diluent for continuous administration. Its high aqueous solubility relative to morphine salts is the practical reason for its use in palliative-care syringe drivers.

  3. Reaching the cell

    Crosses into the brain several times faster than morphine

    The two acetyl groups make the molecule much greasier, so it slips through the blood-brain barrier far more quickly than morphine can.

    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

    Acetylation at the 3- and 6-positions raises lipophilicity substantially, increasing the rate of blood-brain barrier penetration by roughly an order of magnitude over morphine. This rate difference, not a receptor difference, is what produces the characteristic rapid onset.

  4. The change it makes

    Deacetylated to 6-monoacetylmorphine and then to morphine

    Enzymes strip off the added groups within minutes. What ends up on the receptor is morphine, plus an intermediate that is itself a strong opioid.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Plasma and tissue esterases hydrolyse diacetylmorphine to 6-monoacetylmorphine within minutes, then more slowly to morphine. 6-MAM is a potent mu agonist and is the analyte that proves heroin exposure specifically, because it has no other source.

  5. What it acts on

    Mu-opioid receptors are activated across pain, reward and respiratory circuits

    The receptor sits in the pain pathways, the reward pathways and the part of the brainstem that sets breathing rate. It is activated in all three at once.

    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

    Mu-opioid receptor agonism in the periaqueductal grey and spinal dorsal horn produces analgesia; in the ventral tegmental area, reward; in the pre-Bötzinger complex, dose-dependent suppression of respiratory drive. The therapeutic and the lethal effect are the same receptor in different tissue, which is why no mu agonist has separated them.

  6. What that does for a person

    Analgesia, or retention in treatment, or respiratory arrest

    In a hospital it relieves severe pain. In a supervised clinic it keeps people in treatment. Unsupervised, in a supply of unknown composition, it stops breathing.

    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 across this page: licensed analgesic use in the UK; 72% versus 27% street-heroin-negative urines in RIOTT; 87.8% versus 54.1% treatment retention in NAOMI. Respiratory depression is dose-dependent and reversible by naloxone, which competitively displaces the agonist — a fact that does not extend to xylazine-adulterated supply.

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

Felt, measured, or meaningful

Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.

Felt

Things a person could notice without a test.

No registered study measured anything of this kind.

Measured

Things only a test, a scale or a device shows.

  • plasma soluble cd14 concentration
  • plasma interferon gamma induced protein 10 concentration
  • plasma intestinal fatty acid binding protein concentration

Meaningful

Things that change how a life goes, not only a number.

No registered study measured anything of this kind.

A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.

Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.

Measured, but not felt. A number moves. The person notices nothing. Both can be true.

Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.

Matters, but takes years. The result that counts may take longer than anyone would keep watching.

Names that fit none of the three (2)
  • brain functions
  • endopat measure of microvascular function

These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.

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.

  • In UK medicine: patients with severe acute pain, myocardial infarction, terminal illness or acute pulmonary oedema. In heroin-assisted treatment: people with long-standing opioid dependence who have failed repeated conventional treatment including methadone. Outside medicine: an illicit market in which the substance sold as heroin increasingly is not heroin.

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.

Where the result stopped carrying

  • Supervised injectable methadone, the intermediate arm of RIOTT, did not separate significantly from optimised oral methadone
  • Bayer marketed heroin from 1898 as a cough remedy and a supposedly non-addictive morphine substitute; the non-addictive claim was wrong and the US banned medical use in 1924
  • 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 for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

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 (10)
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

Not available

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

Injection — intravenous, intramuscular or subcutaneous; freeze-dried powder for reconstitution

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

RNAWiki has not recorded a supervision or regulatory status for this substance.

Quoted from a source

Where this came from

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

No register row and no identity class settled the question.

No source is stored against this line.

What is in the pack

The UK medicine is a sterile freeze-dried powder reconstituted before use.

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. The rest of the recorded wording: Its high solubility means a large opioid dose fits in a small volume, which is the practical reason palliative-care services use it in subcutaneous syringe drivers where morphine salts would need several times the fluid. In heroin-assisted treatment the injection is given in a licensed clinic, witnessed, with medical staff and resuscitation equipment present — a requirement that came directly out of the overdose and seizure events recorded in the trials.

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

Class effects of a mu-opioid agonist: dose-dependent respiratory depression, sedation, miosis, constipation, nausea, pruritus and urinary retention, with tolerance developing to most of them except constipation and miosis. Respiratory depression is the fatal mechanism and is reversible by naloxone. Physical dependence develops with repeated use and abrupt cessation produces a withdrawal syndrome that is severely unpleasant and not usually life-threatening in otherwise healthy adults, in contrast to alcohol or benzodiazepine withdrawal. In the supervised trials, overdose and seizure occurred at measurable rates even with pharmaceutical-grade material of known strength, which is the argument for supervision rather than against the treatment.

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

Where this came from

Reports sent to a regulator

  • These are reports people sent to a regulator. They do not show the medicine caused the reaction.
  • Nobody counted how many people took the medicine and reported nothing.
  • The same event can be reported more than once, and many reports are incomplete.
  • News coverage, lawsuits and new warnings change how often people report.
  • A count is not a rate and not a risk.

Diamorphine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 110 reaction mentions were counted. One report can name several reactions.

The recorded terms (10)
  • drug abuse — 16 reaction mentions
  • toxicity to various agents — 15 reaction mentions
  • drug withdrawal syndrome neonatal — 11 reaction mentions
  • hypotension — 11 reaction mentions
  • confusion postoperative — 10 reaction mentions
  • mental status changes postoperative — 10 reaction mentions
  • metabolic alkalosis — 10 reaction mentions
  • unevaluable event — 10 reaction mentions
  • myoclonus — 9 reaction mentions
  • premature baby — 8 reaction mentions
  • open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot

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 unclearNothing found in the sources checked

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

Injection — intravenous, intramuscular or subcutaneous; freeze-dried powder for reconstitution

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

A recorded note compares this form with the others that are sold. It is kept below, word for word.

A fixed RNAWiki sentence

Where this came from

Wording RNAWiki always uses, not a finding about this substance.

The recorded note, unchanged: Its high solubility means a large opioid dose fits in a small volume, which is the practical reason palliative-care services use it in subcutaneous syringe drivers where morphine salts would need several times the fluid. In heroin-assisted treatment the injection is given in a licensed clinic, witnessed, with medical staff and resuscitation equipment present — a requirement that came directly out of the overdose and seizure events recorded in the trials.

No source is stored against this line.

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.

RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.

Questions worth asking

  • Which of the trials of Diamorphine 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 heroin binds the mu receptor more strongly than morphine — it is a prodrug with low intrinsic affinity, and the difference is rate of brain entry

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 the trial results generalise beyond people who have already failed conventional treatment; no trial enrolled an unselected population

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 risk figures for diacetylmorphine describe the material now sold as heroin, which frequently contains fentanyl analogues, nitazenes or xylazine

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 Schedule I status reflects an assessment that medical use is impossible, when the same molecule is licensed elsewhere

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.

How much did people take in the studies?

The sources RNAWiki checked hold nothing for this field.

Why it matters. A result belongs to an amount. Without the amount the result floats free.

What would answer it

A stored source that records 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.

How fast does the body clear it?

The sources RNAWiki checked hold nothing for this field.

Why it matters. Without this, nothing on this page can say how long anything lasts.

What would answer it

A stored source that records 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 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 Diamorphine 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.

Schedule I in the United States, a licensed medicine in the United Kingdom
In plain words
The US classifies heroin as having no accepted medical use. The UK licenses it for heart attack pain, surgical pain, terminal illness and acute heart failure, and carries it in ambulances.
What was measured
Existence of a licensed medical indication for the same molecule in two jurisdictions
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Heroin is listed in Schedule I of the United States Controlled Substances Act at 21 CFR 1308.11(c), a schedule defined by high abuse potential, no currently accepted medical use in the United States, and lack of accepted safety for use under medical supervision. In the United Kingdom, Diamorphine Hydrochloride for Injection holds a marketing authorisation with the licensed indications "severe pain associated with surgical procedures, myocardial infarction or pain in the terminally ill and for the relief of dyspnoea in acute pulmonary oedema"; it is a Class A drug under the Misuse of Drugs Act 1971 and sits in Schedule 2 of the Misuse of Drugs Regulations 2001, the schedule for controlled drugs with recognised medical use. Two regulators, one molecule, opposite findings on the single question of whether an accepted medical use exists. The disagreement is not scientific: the UK use is documented and the US finding is a legal determination that has not been revisited for this substance.
Source
21 CFR 1308.11(c); Diamorphine Hydrochloride for Injection Summary of Product Characteristics, section 4.1, UK electronic Medicines Compendium
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
RIOTT: supervised injectable heroin beat oral methadone with a number needed to treat of 2.2
In plain words
In 127 long-term users who kept injecting street heroin despite being on methadone, supervised medical heroin got 72% off street heroin against 27% on optimised oral methadone.
What was measured
Proportion with 50% or more street-heroin-negative weekly urine specimens, weeks 14 to 26
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Multisite, open-label randomised controlled trial in three supervised injecting clinics in England. 127 chronic heroin users, all on conventional oral treatment for at least six months and still injecting street heroin on at least half of days in the preceding three months, randomised to supervised injectable methadone (n=42), supervised injectable heroin (n=43) or optimised oral methadone (n=42) for 26 weeks. Primary outcome was 50% or more negative weekly urine specimens for street heroin during weeks 14 to 26. At 26 weeks, 80% remained in assigned treatment: 81% injectable methadone, 88% injectable heroin, 69% oral methadone. Primary outcome achieved by 72% on injectable heroin versus 27% on oral methadone (OR 7.42, 95% CI 2.69 to 20.46, p<0.0001; adjusted 66% versus 19%, OR 8.17, 2.88 to 23.16, p<0.0001), number needed to treat 2.17 (95% CI 1.60 to 3.97). Injectable methadone versus oral methadone was not significant (OR 1.74, 95% CI 0.66 to 4.60, p=0.264). Differences appeared within the first six weeks. ISRCTN01338071.
Source
Strang J et al., Lancet 2010;375:1885-1895 (RIOTT, ISRCTN01338071)
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
NAOMI: 88% retention against 54% on methadone, with overdoses in the heroin arm
In plain words
A Canadian trial in 226 people who had failed treatment twice found injectable heroin kept far more of them in treatment — and produced ten overdoses and six seizures that supervision caught.
What was measured
Retention in addiction treatment at 12 months, intention to treat
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Open-label phase 3 randomised controlled trial in Canada comparing injectable diacetylmorphine (115 patients) with oral methadone maintenance (111 patients) in long-term injecting heroin users who had failed at least two previous treatment attempts including at least one methadone treatment. Primary outcomes at 12 months were retention in addiction treatment or drug-free status, and reduction in illicit-drug use or other illegal activity on the European Addiction Severity Index; outcomes were determined in 95.2% of participants. Intention-to-treat retention was 87.8% with diacetylmorphine versus 54.1% with methadone (rate ratio 1.62, 95% CI 1.35 to 1.95, P<0.001). Reduction in illicit-drug use or other illegal activity was 67.0% versus 47.7% (rate ratio 1.40, 95% CI 1.11 to 1.77, P=0.004). The most common serious adverse events with diacetylmorphine were overdoses in 10 patients and seizures in 6. The authors' conclusion includes the constraint: this treatment must be delivered where prompt medical intervention is available.
Source
Oviedo-Joekes E et al. Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction. N Engl J Med 2009;361:777-786 (NCT00175357)
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
Cochrane: the benefit is real, and it is confined to people conventional treatment failed
In plain words
The systematic review concluded heroin maintenance helps a specific group — people who have already failed methadone — and should be delivered in supervised clinics because of the overdose risk.
What was measured
Pooled retention and illicit-use outcomes across randomised heroin maintenance trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Ferri, Davoli and Perucci reviewed randomised controlled trials of heroin maintenance versus other maintenance treatments in chronic heroin-dependent individuals for the Cochrane Database of Systematic Reviews. The review's scope is deliberately narrow: it addresses supervised injectable heroin as a second-line treatment for people not benefiting from methadone, not as a first-line option, and it records the serious adverse events — including overdose during supervised administration — that define the delivery requirements. The consistent finding across the European and Canadian trials is retention and reduction in street-drug use, in a population selected for prior treatment failure. Generalising the result to unselected opioid-dependent populations is not supported by any of the included trials, because none of them enrolled one.
Source
Ferri M, Davoli M, Perucci CA. Heroin maintenance for chronic heroin-dependent individuals. Cochrane Database Syst Rev 2011;(12):CD003410
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
Heroin is a prodrug and is weaker than morphine at the receptor it is famous for
In plain words
Diamorphine barely binds the opioid receptor. It gets into the brain fast and is converted there into morphine, which does the binding.
What was measured
Mu-opioid receptor affinity of diacetylmorphine versus 6-monoacetylmorphine versus morphine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Diacetylmorphine has low affinity at the mu-opioid receptor relative to morphine in binding assays run with esterase activity blocked. In vivo, plasma and tissue esterases deacetylate it within minutes to 6-monoacetylmorphine — a potent mu agonist that crosses the blood-brain barrier readily — and then to morphine. The two acetyl groups raise lipophilicity enough to increase the rate of central nervous system entry several-fold over morphine, which is the whole of the difference in onset. The clinical consequences follow: analgesic potency by injection is higher than morphine on a milligram basis, the receptor pharmacology is morphine's, and the higher aqueous solubility of the hydrochloride is why palliative-care services value it for subcutaneous infusion in small volumes.
Source
Standard opioid pharmacology; UK Diamorphine Hydrochloride for Injection SmPC, pharmacological properties; forensic 6-MAM interpretation literature
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
What is sold as heroin now often is not heroin, and the risk figures have not caught up
In plain words
The illicit supply in North America is increasingly fentanyl, nitazenes and xylazine rather than heroin. Statements about heroin overdose risk drawn from older data are describing a different drug.
What was measured
That overdose risk, potency and naloxone responsiveness figures for diacetylmorphine describe the material currently sold as heroin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Every dose-response, overdose-risk and treatment-outcome figure on this page was generated with analytically confirmed diacetylmorphine — pharmaceutical-grade in the trials, or opium-derived material of measured purity in the epidemiology. The substance now sold as heroin in much of North America contains illicitly manufactured fentanyl and its analogues, benzimidazole opioids of the nitazene class, and the veterinary alpha-2 agonist xylazine, in combinations that vary between batches. Those have different potencies, different durations, and in the case of xylazine no response to naloxone. The inference that fails is the ordinary one a reader would make: that risk information about heroin describes the risk of what is being sold as heroin. Each of those adulterants has its own record on this site.
Source
Composition of the illicit opioid supply — see the fentanyl, nitazene and xylazine records on this site for the primary sources
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

Where else this substance is registered

FDA substance identifier (UNII)
70D95007SX
CAS registry number
561-27-3
PubChem compound
5462328
ChEMBL
CHEMBL459324
ChEBI
27808
RxNorm concept
3304
EMA substance identifier
100000079547
European Chemicals Agency number
209-217-7
DrugBank
DB01452

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What is missing or unclearRead from sources, not yet reviewed

What to learn next

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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.

The same molecule is a licensed injectable medicine in the United Kingdom and a Schedule I substance with no accepted medical use in the United States, and randomised trials in two countries found supervised injectable heroin retained treatment-refractory patients better than oral methadone.

Recorded evidence blocks (7)

What did Diamorphine's largest trial (1015 people) and its longest (5.8 years) measure?


1015 people in Diamorphine's largest registered study, 5.8 years in its longest registered window, measuring Change in plasma soluble CD14 concentration. ClinicalTrials.gov · 2026-09-01

3 phase3, 2 na, 1 na or unstated, 1 phase1; NCT00268814; 2007-12; no ageing endpoint recorded. Last human test completed 2022, NCT03976258.

Interpretation These counts include studies where Diamorphine was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase3
    3
  • na
    2
  • na or unstated
    1
  • phase1
    1
  • Last recorded human test NCT03976258
    2022-12-31

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

Diamorphine was tested only in human — what did it show?


human: biomarker (7): the rungs where Diamorphine has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Change in plasma soluble CD14 concentration — the recorded outcome words.

Yeast C. elegans Drosophila Mouse Rat Dog Non-human primate Human biomarker
Show the evidence
  • human NCT03976258
    biomarker; Change in plasma soluble CD14 concentration; 7

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

Could one person measure Diamorphine's effect on brain functions?


Brain functions: measured in Diamorphine's trials.

Interpretation brain functions is the recorded endpoint.

Show the evidence

biomarkers

  • brain functions; 2026-09-01
  • plasma soluble cd14 concentration; 2026-09-01
  • endopat measure of microvascular function; 2026-09-01
  • plasma interferon gamma induced protein 10 concentration; 2026-09-01
  • plasma intestinal fatty acid binding protein concentration; 2026-09-01
  • human trials at or under30
    2
  • Not recorded for this substance
    a recorded half-life
  • smallest human trial
    18; NCT01049672; NA; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; COMPLETED

Which of brain functions, endopat measure of microvascular function and plasma interferon gamma induced protein 10 concentration did Diamorphine's trials measure?


brain functions, endopat measure of microvascular function and plasma interferon gamma induced protein 10 concentration lead 5 outcome terms across Diamorphine's trials. ClinicalTrials.gov · 2026-09-01

plasma interferon gamma induced protein 10 concentration and plasma intestinal fatty acid binding protein concentration follow.

Show the evidence
  • brain functions
    1
  • plasma soluble cd14 concentration
    1
  • endopat measure of microvascular function
    1
  • plasma interferon gamma induced protein 10 concentration
    1
  • plasma intestinal fatty acid binding protein concentration
    1

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

Which 6 trials of Diamorphine posted no result?


Posted no result
6 of 6 completed trials
Registrations
NCT00268814, NCT00175357, NCT01174927, NCT01049672, NCT02210260 and NCT03976258
Completion dates
oldest 2007-12; newest 2022-12-31
Show the evidence

Trial

  • NCT00268814
    2007-12
  • NCT00175357
    2009-04
  • NCT01174927
    2012-02
  • NCT01049672
    2014-11
  • NCT02210260
    2016-02
  • NCT03976258
    2022-12-31

At the median, Diamorphine's trials enrolled 79 people — anything larger?


Median enrolment
79
Largest enrolment
1015
Registered trials counted
7

What do 110 spontaneous reports say about Diamorphine — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

Diamorphine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 110 reaction mentions were counted: drug abuse 16; toxicity to various agents 15; drug withdrawal syndrome neonatal 11; hypotension 11. open-targets-adr · CHEMBL2106627 · 2026-06-24

Show the evidence
  • drug abuse
    16
  • toxicity to various agents
    15
  • drug withdrawal syndrome neonatal
    11
  • hypotension
    11
  • confusion postoperative
    10
  • mental status changes postoperative
    10
4 more recorded rows
  • metabolic alkalosis
    10
  • unevaluable event
    10
  • myoclonus
    9
  • premature baby
    8

recorded 2026-06-24 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL2106627
PubChem CID
5497159
CAS number
1502-95-0
RxCUI
81994
InChIKey
GVGLGOZIDCSQPN-PVHGPHFFSA-N
Also called
Heroin (Diamorphine, Diacetylmorphine)
Also called
DIACETYLMORPHINE HYDROCHLORIDE, NSC-302357, DIACETYLMORPHINE, dam, (5.ALPHA.,6.ALPHA.)-7,8-DIDEHYDRO-4,5-EPOXY-17-METHYLMORPHINAN-3,6-DIOL DIACETATE (ESTER), ACETOMORPHINE, CHINA WHITE, DIACETYLMORPHINE [MI], DIAPHORM, Diamorphine [WHO-DD], ECLORION, HEROIN [HSDB]
Salt form
Diacetylmorphine hcl, Diacetylmorphine hydrochloride ci, Diamorphine hydrochloride, Diamorphine Hydrochloride for Injection — a licensed medicine in the United Kingdom. Originally marketed by Bayer as Heroin from 1898
Development code
IDS-NH-001, J6.494G
Component
Heroin (Diamorphine, Diacetylmorphine)
Sources (5)

Sources

ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md

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