This page shows what was measured, who it was measured in, and what that does not settle.
What Methadone does in the body
Opioid dependence, as maintenance or detoxification treatment; and severe long-term pain
Methadone is a synthetic opioid that does not look like morphine but binds the same receptor. What makes it different is how long it lasts: taken once a day it holds a steady level, so there is no cycle of rush and withdrawal, and enough receptor is occupied that another opioid on top produces much less effect. The problem is the same property. Methadone leaves the body at a rate that varies enormously between people — its own label reports a half-life anywhere from eight to fifty-nine hours — so it accumulates over days, and the label warns that its peak effect on breathing comes later and lasts longer than its peak painkilling effect. It also blocks a potassium channel in the heart, which can lengthen the electrical cycle and trigger a dangerous rhythm.
What happened in people
Methadone involved in 31.4% of opioid pain reliever deaths in 13 states while accounting for 4.5% to 18.5% of opioids distributed by state
✎ 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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
The limit that matters most
That methadone maintenance has a demonstrated randomised mortality benefit — the point estimate favours it, the confidence interval does not exclude harm, and the case rests on cohort data
Where it acts
Mu-opioid receptors of the brain and spinal cord; and the hERG potassium channel of cardiac myocytes, which is where the boxed cardiac warning comes from
Kind of result
Symptoms and quality of life
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 C21H27NO•HCl, weighing 345.91.
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
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.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 171 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
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 people◇Read 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 heroin use with methadone maintenance against treatments not using opioid replacement, in opioid dependence
✓ The study showed what it set out to show
Who was studied
Cochrane CD002209 — 11 randomised trials of methadone maintenance
How many people
1969
Study design
Systematic review and meta-analysis of randomised clinical trials, two of them double-blind
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Heroin use RR 0.66 (95% CI 0.56 to 0.78) across 6 RCTs; retention significantly better; criminal activity RR 0.39 (0.12 to 1.25) and mortality RR 0.48 (0.10 to 2.39), neither statistically significant
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. Sequence generation was inadequate in one included study and unclear in several; allocation concealment was adequate in only three. The mortality analysis rests on four trials and its confidence interval spans a five-fold reduction to a two-fold increase — the outcome most often attributed to methadone is the one the randomised evidence is least able to resolve.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
All-cause and overdose mortality per 1,000 person-years during and outside methadone treatment in people with opioid dependence
✓ The study showed what it set out to show
Who was studied
Sordo et al., BMJ 2017;357:j1550 — pooled cohort mortality analysis
How many people
122885
Study design
Systematic review and multivariate random-effects 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
All-cause mortality 11.3 in against 36.1 out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% CI 2.65 to 3.86); overdose mortality 2.6 against 12.7 (4.80, 2.90 to 7.96)
Repeated elsewhere
Partially 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. These are cohort data, not randomised. The authors state that further research must properly account for potential confounding and selection bias, both between treatments and across periods in and out of treatment. All-cause mortality dropped sharply only over the first four weeks of methadone treatment, so induction is a period of elevated rather than reduced risk, as are the weeks immediately after leaving.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
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 it changes in the body◇Read 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.
Where a source records it acting
Brain: Mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involve the central nervous system
US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27
Brainstem: Produces respiratory depression by direct action on brain stem respiratory centers
US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27
Stomach: Causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum
US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27
Start
Methadone
What a person takes: Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8..
The measurement behind this step
Once-daily oral dosing is possible because of a terminal half-life the label reports between 8 and 59 hours, and that same range is why steady state is reached at an unpredictable time. Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. Because it is a base of pKa 9.2, urinary pH alters its disposition.
Getting in
Not a poppy molecule at all
Methadone looks nothing like morphine. It is a fully synthetic compound built from two benzene rings and a short chain, which happens to fold into the shape the opioid receptor recognises.
╌╌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
A diphenylheptanone, C21H27NO, with no morphinan ring system. Marketed as the racemate: R-methadone carries essentially all the mu agonism, S-methadone most of the hERG potassium channel block.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
Reaching the cell
It goes into tissue and comes back out slowly
Being fat-soluble, methadone loads into the liver and other tissues and leaks back out for days. That is why one dose lasts and why several doses stack up.
──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
The label notes methadone is lipophilic and known to persist in liver and other tissues, and that slow release from those tissues may prolong its action despite low plasma concentrations. Terminal half-life 8 to 59 hours and apparent clearance 1.4 to 126 L/h across published studies; being a base of pKa 9.2, urinary pH alters disposition.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
What it acts on
Steady occupancy of the mu receptor
Instead of a peak and a crash, methadone holds the receptor at a steady level. No rush, no withdrawal, and enough occupancy that another opioid on top does much less.
╌╌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
Full mu agonism with a pharmacodynamic profile qualitatively similar to morphine; the label notes the withdrawal syndrome is slower in onset, longer in course and less severe in symptoms than morphine’s. Some data indicate NMDA receptor antagonism, whose contribution to efficacy the label states is unknown.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
The change it makes
Five liver enzymes, and everything interacts
Methadone is broken down by five different liver enzymes. Almost any new medicine can raise or lower its level, and the boxed warning names all five.
╌╌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
Hepatic N-demethylation to inactive EDDP by CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6. The boxed warning states that concomitant use with inhibitors of any of them may increase methadone concentrations and cause potentially fatal respiratory depression, and that inducers may reduce effect and precipitate withdrawal.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
What that does for a person
And a potassium channel in the heart
The same molecule blocks a channel that resets the heart’s electrical cycle. Lengthen that cycle enough and a lethal rhythm becomes possible.
──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
hERG potassium channel block, more potent for S-methadone than R-methadone. Boxed warning for QT prolongation and torsades de pointes, most cases at large multiple daily analgesic doses but reported at maintenance doses too. The founding case series: 17 patients, mean daily dose 397 ± 283 mg, mean QTc 615 ± 77 ms.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
What that does for a person
What treatment actually changes
Randomised trials show people stay in treatment and use less heroin. The much larger observational record shows death rates roughly a third of those out of treatment — a finding its own authors flag for confounding.
──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
Cochrane CD002209, 11 RCTs, 1,969 participants: heroin use RR 0.66 (95% CI 0.56 to 0.78); mortality RR 0.48 (0.10 to 2.39), not significant. Sordo BMJ 2017, 19 cohorts, 122,885 methadone patients: all-cause mortality 11.3 against 36.1 per 1,000 person-years in against out of treatment; overdose mortality 2.6 against 12.7.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 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 unclear◇Read 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.
People in opioid maintenance or detoxification programmes, dispensed under a specific federal regulatory framework in the United States; and a much smaller number of people with severe chronic pain.
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, effectiveness, and pharmacokinetics of methadone in pediatric patients below the age of 18 years have not been established.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
On older people, the label states: “Clinical studies of methadone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary The majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Based on two small clinical studies, methadone was present in low levels in human milk, but the exposed infants in these studies did not show adverse reactions.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
On people with reduced liver function, the label states: “Methadone pharmacokinetics have not been extensively evaluated in patients with hepatic insufficiency.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
On people with reduced kidney function, the label states: “Methadone pharmacokinetics have not been extensively evaluated in patients with renal insufficiency.”
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-30
Where the result stopped carrying
Mortality and criminal activity as randomised endpoints, neither reaching statistical significance across the available trials
Methadone as a cheap first-line long-acting analgesic, which CDC concluded should not be a drug of first choice for chronic non-cancer pain
The assumption that a long half-life is simply convenient, when the peak respiratory depressant effect arrives after the peak analgesic effect
Levacetylmethadol, a methadone derivative withdrawn from the European market after association with torsades de pointes, which is the fact the original QT case series opens with
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 take◇Read 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 take◇Read 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
Prescription only
❝ 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
Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.
✎ 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, S2, S5, S6.
No source is stored against this line.
What is in the pack
Once-daily oral dosing is possible because of a terminal half-life the label reports between 8 and 59 hours, and that same range is why steady state is reached at an unpredictable time.
✎ 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: Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. 2, urinary pH alters its disposition.
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 take◇Read 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
Boxed warnings for life-threatening respiratory depression during initiation and conversion, including in patients using the drug as directed; life-threatening QT prolongation and torsades de pointes; fatal overdose from accidental ingestion, especially by children; abuse potential comparable to other opioid agonists; interactions with drugs affecting CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6; concomitant benzodiazepines and other CNS depressants; and the regulatory conditions for treatment of opioid addiction. The label states that the peak respiratory depressant effect occurs later and persists longer than the peak pharmacologic effect, especially during initial dosing — the single most important sentence on the document.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal W… · 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 unclear◇Read 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
Oral tablets, dispersible tablets for oral suspension, concentrated oral solution and injection. Schedule II controlled substance in the United States; for opioid addiction, distribution and use are subject to 42 CFR Part 8.
✎ 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
Being lipophilic, methadone loads into liver and other tissue and releases slowly, which the label notes may prolong its action despite low plasma concentrations. 2, urinary pH alters its disposition.
✎ 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
62 products list this as an active ingredient in the United States drug directory. 62 of them contain it and nothing else.
FDA National Drug Code directory · 72865-120 · read 2026-08-29
They are sold as concentrate, injection, injection, solution, powder, solution and tablet, taken intramuscular, intravenous, oral and subcutaneous.
FDA National Drug Code directory · 72865-120 · read 2026-08-29
The regulator's established pharmacologic class for it is full opioid agonists [moa] and opioid agonist [epc].
FDA National Drug Code directory · 72865-120 · read 2026-08-29
36 published labels name it as an active ingredient. 36 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 50f14803-78c0-4d19-8b5d-9a9c17582ac1 · read 2026-08-29
1 marketed supplement label lists this ingredient, classed as botanical with nutrients.
Those labels carry all other and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Methadone Hydrochloride is injection (multiple-dose vials) at 200 mg/20 mL (10 mg/mL), recorded as prescription opioid; fda label in effect 2025-12-31 in the United States.
US prescribing information · 092d78eb-6423-495c-bf0d-e6532bea7138 · read 2026-08-27
Recorded price in US: 0.16625–0.17521 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 19 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
Recorded price in US: 0.55399 USD per one millilitre, across 2 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 take◇Read 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 Methadone 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 unclear◇Read 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 methadone maintenance has a demonstrated randomised mortality benefit — the point estimate favours it, the confidence interval does not exclude harm, and the case rests on cohort data
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 NMDA receptor antagonism gives methadone an advantage in neuropathic or opioid-tolerant pain, when the label states that contribution is unknown
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 a stated methadone dose corresponds to a predictable exposure, given a reported ninety-fold range in apparent clearance
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 cohort comparison of methadone against buprenorphine mortality ranks the two drugs, when the populations were never randomised against each other
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 unclear◇Read 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 Methadone 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 people◇Read 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.
The randomised evidence shows retention, not survival
In plain words
Eleven randomised trials in nearly two thousand people found methadone kept more of them in treatment and cut heroin use. On deaths, and on crime, the difference did not reach statistical significance.
What was measured
Retention in treatment, heroin use, criminal activity and mortality, methadone maintenance against non-pharmacological treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mattick and colleagues included 11 randomised clinical trials, two of them double-blind, totalling 1,969 participants. Methadone was statistically significantly more effective than non-pharmacological approaches at retaining patients in treatment and at suppressing heroin use measured by self-report and urine or hair analysis (6 RCTs, RR 0.66, 95% CI 0.56 to 0.78). It was not statistically different on criminal activity (3 RCTs, RR 0.39, 95% CI 0.12 to 1.25) or on mortality (4 RCTs, RR 0.48, 95% CI 0.10 to 2.39). Sequence generation was inadequate in one study and unclear in several; allocation concealment was adequate in only three. The point estimates for crime and mortality both favour methadone substantially and both have confidence intervals crossing one, which is what four small trials look like when the outcome is rare. The reviewers’ conclusion states it precisely: methadone retains patients and decreases heroin use better than treatments without opioid replacement, and does not show a statistically significant superior effect on criminal activity or mortality.
Written into the record, not signed off as a reviewed claim
The mortality case is enormous, consistent, and observational
In plain words
Nineteen cohorts following almost 123,000 people on methadone found death rates roughly a third of those seen out of treatment. The authors themselves say further work is needed to account for confounding and selection, because people are not randomly assigned to be in or out of treatment.
What was measured
All-cause and overdose mortality per 1,000 person-years in and out of methadone treatment across 122,885 patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sordo and colleagues pooled 19 eligible cohorts following 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 11.3 per 1,000 person-years in methadone treatment and 36.1 out of it (unadjusted out-to-in rate ratio 3.20, 95% CI 2.65 to 3.86), and 4.3 against 9.5 for buprenorphine (2.20, 1.34 to 3.61). Pooled overdose mortality was 2.6 in and 12.7 out of methadone treatment (rate ratio 4.80, 2.90 to 7.96) and 1.4 against 4.6 for buprenorphine. In trend analysis, all-cause mortality dropped sharply over the first four weeks of methadone treatment and rose in the two weeks after leaving treatment; on buprenorphine it remained stable during induction. The authors state that these findings are potentially important but that further research must properly account for potential confounding and selection bias in comparisons of mortality risk between treatments and across periods in and out of them. The inference this supports is that retention is associated with far lower mortality. The inference it does not license, on its own, is a causal effect size, or a head-to-head ranking of methadone against buprenorphine.
Written into the record, not signed off as a reviewed claim
A few per cent of prescriptions, a third of the deaths
In plain words
When methadone was widely prescribed as a cheap long-acting painkiller, it accounted for a small share of opioid prescribing and about a third of prescription opioid overdose deaths.
What was measured
Share of opioid pain reliever overdose deaths involving methadone against its share of opioids distributed, 13 states, 2009-2010
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CDC analysed fatal methadone overdoses and sales nationally over 1999 to 2010 and overdose death rates in 13 states for 2009. Methadone overdose deaths and sales rates peaked in 2007. In 2010 methadone accounted for between 4.5% and 18.5% of the opioids distributed by state. It was involved in 31.4% of opioid pain reliever deaths in the 13 states and accounted for 39.8% of single-drug opioid pain reliever deaths, with an overdose death rate significantly greater than that of other opioid pain relievers for both multidrug and single-drug deaths. The mechanism is in the label: the peak respiratory depressant effect occurs later and persists longer than the peak analgesic effect, and terminal half-life ranges from 8 to 59 hours across studies, so a patient titrating by feel accumulates. CDC concluded that methadone should not be used for mild pain, acute pain, breakthrough pain or on an as-needed basis, and that for chronic non-cancer pain it should not be considered a drug of first choice by prescribers or insurers. That last clause names the actual driver: methadone was being selected on formularies because it was cheap.
Source
Centers for Disease Control and Prevention. Vital signs: risk for overdose from methadone used for pain relief — United States, 1999-2010. MMWR Morb Mortal Wkly Rep 2012;61(26):493-497
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
It blocks a cardiac potassium channel, and the label says so in a box
In plain words
Methadone lengthens the heart’s electrical recovery and can trigger a lethal rhythm. The case series that established this reported seventeen patients with an average corrected QT of 615 milliseconds — well over the usual danger threshold.
What was measured
Corrected QT interval and daily methadone dose in 17 patients who developed torsades de pointes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Krantz and colleagues reported a retrospective case series of 17 methadone-treated patients from United States maintenance programmes and a Canadian pain centre who developed torsades de pointes. Mean daily methadone dose was 397 ± 283 mg and mean corrected QT interval was 615 ± 77 ms. Fourteen had a predisposing risk factor for arrhythmia, 14 received a defibrillator or pacemaker, and all 17 survived. The paper opens by noting that a methadone derivative, levacetylmethadol, had already been withdrawn from the European market after association with torsades. The current methadone label carries this as a boxed warning: QT interval prolongation and serious arrhythmia have occurred during treatment, most cases involving patients treated for pain with large multiple daily doses, although cases have been reported at doses commonly used for maintenance treatment of opioid addiction. Mechanistically the racemate’s S-enantiomer is the more potent blocker of the hERG potassium channel while the R-enantiomer carries the opioid effect, so the cardiac liability travels with a component that is not doing the therapeutic work.
Written into the record, not signed off as a reviewed claim
The NMDA story is on the label, and the label says its value is unknown
In plain words
Methadone is often described as uniquely useful in nerve pain because it also blocks a second receptor called NMDA. The prescribing information states that some data indicate it does, and that what that contributes to the drug’s effect is unknown.
What was measured
That NMDA receptor antagonism gives methadone a clinical advantage in neuropathic or opioid-tolerant pain — a mechanism the label acknowledges and whose contribution to efficacy it states is unknown
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.1 of the methadone label reads: "Methadone hydrochloride is a mu-agonist; a synthetic opioid with multiple actions qualitatively similar to those of morphine... Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown." The clinical claim built on that sentence — that methadone succeeds in neuropathic pain, or in opioid-tolerant patients, where other opioids fail, because of NMDA blockade — is a mechanism-to-outcome inference the regulator declines to make. It also sits awkwardly with the enantiomer picture: the NMDA antagonism is generally attributed to S-methadone, the same enantiomer that carries most of the hERG liability and little of the opioid agonism. Whether the marketed racemate delivers enough NMDA blockade at clinical concentrations to matter is the question, and the label’s position is that it is unanswered.
Source
Methadone hydrochloride United States prescribing information, Clinical Pharmacology 12.1
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
A half-life the label cannot give a single number for
In plain words
The prescribing information reports that methadone’s terminal half-life ranged from eight to fifty-nine hours across published studies, and its clearance from 1.4 to 126 litres per hour. That is a ninety-fold spread in clearance for a drug with a narrow safety margin.
What was measured
Reported range of apparent plasma clearance (1.4 to 126 L/h) and terminal half-life (8 to 59 hours) across published multiple-dose studies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label states that after multiple-dose administration, published reports put apparent plasma clearance between 1.4 and 126 L/h and terminal half-life between 8 and 59 hours in different studies. It adds that methadone is a base with pKa 9.2 so urinary pH alters its plasma disposition, and that it is lipophilic enough to persist in the liver and other tissues, with slow release from those tissues potentially prolonging its action despite low plasma concentrations. Hepatic N-demethylation runs through five cytochrome P450 isoforms — CYP3A4, CYP2B6, CYP2C19, CYP2C9 and CYP2D6 — each with its own inhibitors and inducers, which is why the boxed warning names all five. The practical consequence is that steady state is reached at a time nobody can predict for an individual patient, that the peak respiratory depressant effect arrives after the peak analgesic effect, and that a dose which felt too weak on the first day may be lethal on the fourth. This is a pharmacokinetic failure mode rather than a trial failure, and it is the mechanism behind the mortality figures on this page.
Source
Methadone hydrochloride United States prescribing information, Clinical Pharmacology 12.3 and boxed warning
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
36 documents were read for this substance.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
229809935B
CAS registry number
76-99-3
PubChem compound
4095
RxNorm concept
218337
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
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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No internal keys in reader text
enforced by the copy-contract test over the rendered page
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Safety mode resolved
Suppression classes recorded: S1, S2, S5, S6.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read 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
34 approved applications cover products containing this substance. The earliest was NDA021624, approved 19470813 to MYLAN INSTITUTIONAL.
This order is fixed in code and does not count clicks or time on the page.
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.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
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 long-acting mu-agonist that in 11 randomised trials and 1,969 participants beat non-pharmacological treatment on retention and heroin use (RR 0.66, 95% CI 0.56 to 0.78) but not on mortality (RR 0.48, 95% CI 0.10 to 2.39) or crime — while 19 cohorts following 122,885 methadone patients found all-cause mortality of 11.3 per 1,000 person-years in treatment against 36.1 out of it — and whose terminal half-life its own label reports as ranging from 8 to 59 hours across studies, with a boxed warning for torsades de pointes.
Recorded evidence blocks (10)
Q2
On the Methadone label: indicated for what?
"Methadone hydrochloride tablets for oral suspension contain methadone, an opioid agonist indicated for the: Detoxification treatment of opioid addiction (heroin or other morphine-like drugs). Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and…": indications and usage on Methadone's label. DailyMed label · 544483e6-6f9d-4371-9e93-313e54e0ea05 · 2026-08-04
Q3
175 registered trials of Methadone — at which phases?
Registered studies posting no result
134 of 175
175 registered studies of Methadone: 53 phase4, 39 phase3, 34 phase1, 26 phase2, 17 na, 10 na or unstated, 4 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
terminated; "Due to personnel loss and logistical issues the study was unable to be completed as planned."
NCT03134703
terminated; "Poor recruitment"
NCT03908944
withdrawn; "PI- Dr. Jellish passed away. The study was terminated with the IRB"
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Methadone used Methadone HCl Inject 10 mg/ml (will require dilution) — over how long?
studies of Methadone used the recorded amount. ClinicalTrials.gov · 2026-09-01
5 recorded entries; human; IV, oral; also "Methadone HCl Inject 10 mg/ml (will require dilution)", "0.25mg/kg IV of racemic methadone", "Eptadone (1mg/ml) oral solution"
Methadone's half-life is 8 to 59 hours — which schedules were studied?
8 to 59 hours, the half-life Methadone's label states: "Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 to 59 hours in different studies." DailyMed label · 544483e6-6f9d-4371-9e93-313e54e0ea05 · 2026-08-04
tmax 1 to 7.5 hours; bioavailability 36 to 100 %.
Show the evidence
half lifepharmacokinetics
8 to 59 hours; Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 to 59 hours in different studies.
tmaxpharmacokinetics
1 to 7.5 hours; Absorption Following oral administration the bioavailability of methadone ranges between 36 to 100% and peak plasma concentrations are achieved between 1 to 7.5 hours.
bioavailabilitypharmacokinetics
36 to 100 %; Absorption Following oral administration the bioavailability of methadone ranges between 36 to 100% and peak plasma concentrations are achieved between 1 to 7.5 hours.
metabolismpharmacokinetics
Elimination Metabolism : Methadone is primarily metabolized by N-demethylation to an inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene(EDDP).
recorded 2026-08-04 · last checked 2026-09-04
Q7
Which 68 trials of Methadone posted no result?
Posted no result
68 of 68 completed trials
Registrations
NCT00000788, NCT00000200, NCT00000800, NCT00000311, NCT00000906 and NCT00356083, and 62 more
Completion dates
oldest 1994-06; newest 2023-12-31
Show the evidence
Trial
NCT00000788
1994-06
NCT00000200
1998-01
NCT00000800
1998-10
NCT00000311
1999-02
NCT00000906
2000-09
NCT00356083
2005-03
14 further recorded trials
NCT00249587
2005-09
NCT00000273
2005-11
NCT00310934
2006-03
NCT00292123
2006-08
NCT00125294
2007-01
NCT00268814
2007-12
NCT00367302
2008-01
NCT00204243
2008-12
NCT00175357
2009-04
NCT00184496
2009-09
NCT00933283
2009-12
NCT00915564
2010-01
NCT01205256
2010-04
NCT01099748
2010-06
Q8
At the median, Methadone's trials enrolled 54 people — anything larger?
Median enrolment
54
Largest enrolment
27034
Registered trials counted
175
Q9
What do 4257 spontaneous reports say about Methadone — 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.
Methadone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4257 reaction mentions were counted: drug withdrawal syndrome neonatal 1034; toxicity to various agents 538; drug abuse 484; electrocardiogram qt prolonged 461. FAERS via Open Targets · CHEMBL1200825 · 2026-06-24
Show the evidence
drug withdrawal syndrome neonatal
1034
toxicity to various agents
538
drug abuse
484
electrocardiogram qt prolonged
461
somnolence
351
drug interaction
330
4 more recorded rows
coma
324
torsade de pointes
281
respiratory depression
228
drug withdrawal syndrome
226
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Methadone's label not list?
Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6.
drug_interactions
The concomitant use of methadone hydrochloride tablets for oral suspension and CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors can increase the plasma concentration of methadone, resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone hydrochloride tablets for oral suspension is achieved.
drug_interactions
After stopping a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor, as the effects of the inhibitor decline, the methadone plasma concentration can decrease [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or withdrawal symptoms in patients physically dependent on methadone.
drug_interactions
If a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor is discontinued, follow patients for signs of opioid withdrawal and consider increasing the methadone hydrochloride tablets for oral suspension dosage until stable drug effects are achieved.
drug_interactions
Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone hydrochloride tablets for oral suspension and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone.
drug_interactions
After stopping a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer, as the effects of the inducer decline, the methadone plasma concentration can increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression, sedation, or death.
2 more recorded rows
Interaction statementdrug_interactions
If a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer is discontinued, consider methadone hydrochloride tablets for oral suspension dosage reduction and monitor for signs of respiratory depression and sedation.
Interaction statementdrug_interactions
Paradoxical Effects of Antiretroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranavir+ritonavir, has resulted in increased clearance or decreased plasma…
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ 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
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