This page shows what was measured, who it was measured in, and what that does not settle.
What Naloxone does in the body
Emergency reversal of an opioid overdose, when breathing or consciousness has been suppressed
Naloxone is shaped almost exactly like an opioid, so it fits the same receptor. What it does not do is switch the receptor on. It simply sits in the slot and pushes whatever was there out, and it binds tightly enough to win that competition. Within a minute or two of an injection, or a few minutes of a nasal spray, the brainstem starts responding to carbon dioxide again and the person breathes. The catch is duration: naloxone wears off in under an hour and most opioids last longer, so a person can be revived and then stop breathing again once it fades. That is why every label says to call for emergency help and stay with them.
What happened in people
Intranasal naloxone at 2 to 8 mg produced higher plasma concentrations and areas under the curve than an approved 0.4 mg intramuscular dose, with no difference in time to peak
✎ 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.
That the nasal device has been shown to save lives in overdose — no trial in an overdose exists, and none could ethically be run
Where it acts
The mu-opioid receptor of the pre-Bötzinger complex and the brainstem respiratory centres — the site where the overdose is happening
Kind of result
A number that stands in for health
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
15 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · K2KC2UK3AB · 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.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 164 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.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
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.
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.
Plasma naloxone concentration and area under the curve for intranasal naloxone 2 to 8 mg in 0.1 to 0.2 mL against an approved 0.4 mg intramuscular dose, and the ability of untrained members of the public to complete both critical device tasks
✓ The study showed what it set out to show
Who was studied
NCT02572089 (NIDA phase 1 intranasal against intramuscular naloxone; published as Krieter et al., J Clin Pharmacol 2016;56:1243-1253)
How many people
30
Study design
Phase 1, randomised, open-label crossover pharmacokinetic study in healthy volunteers, with a parallel human-factors usability study
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
All intranasal doses produced plasma concentrations and areas under the curve greater than the 0.4 mg intramuscular dose, with no difference in time to maximum concentration; exposure was dose-proportional between 2 and 8 mg; more than 90% of untrained participants completed both critical tasks
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The registered five-arm crossover — intranasal 2 mg, 4 mg from a 20 mg/mL spray in both nostrils, 4 mg from a 40 mg/mL spray in one nostril, and 8 mg, against 1 mL of 0.4 mg/mL intramuscular — enrolled 30 participants and completed in January 2015. Its registered endpoints are Cmax, Tmax, area under the curve and half-life. No overdose outcome was measured in this study or in the parallel usability study, and none could ethically have been: the product is licensed on a pharmacokinetic bridge to a route already known to work, plus evidence that untrained people can operate the device.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intranasal spray at 2, 3, 4 and 8 mg per device; solution for intravenous, intramuscular and subcutaneous injection; a prefilled 5 mg injection; and a single-use auto-injector. Not a controlled substance; the 4 mg nasal spray has been available over the counter in the United States since March 2023.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers — ClinicalTrials.gov NCT02572089, National Institute on Drug Abuse,… · a recorded source, not a stored snapshot
Whether two standard intramuscular or intranasal naloxone doses adequately reverse fentanyl overdose, and whether high-dose naloxone formulations are a better solution
✗ The study did not show it
Who was studied
Lemen et al., Harm Reduct J 2024;21:93 — literature review of standard against high-dose naloxone for fentanyl overdose
How many people
0
Study design
Structured literature review incorporating the experience of people who use drugs
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No pooled effect estimate; the review reports that the vast majority of fentanyl overdoses can be reversed with two standard doses, with carfentanil requiring three or more, and recommends against high-dose formulations
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. A narrative review rather than a meta-analysis, with a sample size of zero recorded because no participants were enrolled. Its finding on precipitated withdrawal — documented in multiple studies at two or more doses, with recurrence of overdose symptoms after resuscitation depending on the half-life of the opioid involved — is the harm that the higher-dose products increase.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intranasal spray at 2, 3, 4 and 8 mg per device; solution for intravenous, intramuscular and subcutaneous injection; a prefilled 5 mg injection; and a single-use auto-injector. Not a controlled substance; the 4 mg nasal spray has been available over the counter in the United States since March 2023.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers — ClinicalTrials.gov NCT02572089, National Institute on Drug Abuse,… · a recorded source, not a stored snapshot
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 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.
Start
Naloxone
What a person takes: Intranasal spray at 2, 3, 4 and 8 mg per device; solution for intravenous, intramuscular and subcutaneous injection; a prefilled 5 mg injection; and a single-use auto-injector. Not a controlled substance; the 4 mg nasal spray has been available over the counter in the United States since March 2023..
The measurement behind this step
Intravenous naloxone acts within about a minute; intramuscular and intranasal within a few minutes. The nasal formulation was developed specifically to be usable by bystanders without training, and the device delivers 0.1 mL into a single nostril. Duration of action is under an hour for most purposes and is shorter than that of most opioids, which is a property of the drug rather than of any particular device.
Getting in
One substitution away from a full agonist
Naloxone is oxymorphone with a different group on its nitrogen. That single change turns a drug that stops breathing into a drug that restores it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Oxymorphone with the N-methyl group replaced by N-allyl, C19H21NO4. The substituent prevents the conformational change that couples receptor occupancy to G-protein activation, so the molecule binds without activating — the cleanest available demonstration that occupancy and efficacy are separate properties.
Into the blood in minutes, by whichever route is available
Injected into muscle or sprayed into the nose, it reaches the blood fast. The nasal device was chosen because it delivers more than a working injection and because untrained people can use it.
──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
Intranasal doses of 2 to 8 mg in 0.1 to 0.2 mL produced plasma concentrations and areas under the curve greater than an approved 0.4 mg intramuscular dose, with no difference in time to peak, and dose-proportional exposure between 2 and 8 mg regardless of whether one or both nostrils were used.
Naloxone binds the mu-opioid receptor tightly enough to push the opioid out, and then simply sits there. Given to someone who has taken no opioid, it does essentially nothing at all.
╌╌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
Competitive antagonism at the mu-opioid receptor with additional kappa and delta antagonism at higher occupancy, and no measurable intrinsic activity. The displacement is surmountable in principle, which is why a very tightly bound partial agonist such as buprenorphine resists it.
The brainstem starts noticing carbon dioxide again
The circuit that had stopped sounding the alarm about rising carbon dioxide comes back online, and the person breathes.
╌╌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
Removal of mu agonism at the pre-Bötzinger complex and the parabrachial and Kölliker-Fuse regions restores the hypercapnic ventilatory response. Effect is visible within about a minute of intravenous administration and a few minutes of intranasal or intramuscular.
Naloxone wears off in under an hour. Most opioids last longer, so breathing can stop again. This is the reason the label’s first warning is to stay and to call for help.
──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
Warning 5.1: due to the duration of action of naloxone relative to the opioid, keep the patient under continued surveillance and administer repeat doses using a new device as necessary while awaiting emergency medical assistance. The gap is largest with methadone, whose label reports a terminal half-life of 8 to 59 hours, and with extended-release products.
In someone dependent on opioids, emptying the receptor abruptly produces severe withdrawal. It is the main argument for giving only as much as is needed to restore breathing.
──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
Warning 5.3: use in opioid-dependent patients may precipitate opioid withdrawal, life-threatening in neonates if not recognised and treated; abrupt postoperative reversal may cause adverse cardiovascular effects. A 2024 review recommends against high-dose formulations as a substitute for four standard doses on cost, precipitated withdrawal and limited evidence.
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 experiencing an opioid overdose. It is carried by bystanders, families, emergency responders and, since 2023 in the United States, anyone who buys it over the counter.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of NARCAN Nasal Spray have been established in pediatric patients of all ages for known or suspected opioid overdose as manifested by respiratory and/or central nervous system depression.”
US prescribing information · 76b5a1ce-e601-457c-ab35-43533bba4394 · read 2026-08-30
On older people, the label states: “Clinical studies of naloxone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 76b5a1ce-e601-457c-ab35-43533bba4394 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary The limited available data on naloxone use in pregnant women are not sufficient to inform a drug-associated risk.”
US prescribing information · 76b5a1ce-e601-457c-ab35-43533bba4394 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There is no information regarding the presence of naloxone in human milk, or the effects of naloxone on the breastfed infant or on milk production.”
US prescribing information · 76b5a1ce-e601-457c-ab35-43533bba4394 · read 2026-08-30
Where the result stopped carrying
The affordability of the delivery devices, with the auto-injector rising more than five-fold in two years while the epidemic accelerated
The premise behind the high-dose formulations, which a 2024 review found unsupported and likely to increase precipitated withdrawal
Reversal of buprenorphine and other tightly bound partial agonists, which the label states may be incomplete
The fifty-year prescription requirement, reversed in March 2023 on the judgement that the barrier caused more harm than the drug
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
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Intranasal spray at 2, 3, 4 and 8 mg per device; solution for intravenous, intramuscular and subcutaneous injection; a prefilled 5 mg injection; and a single-use auto-injector. Not a controlled substance; the 4 mg nasal spray has been available over the counter in the United States since March 2023.
✎ 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
Intravenous naloxone acts within about a minute; intramuscular and intranasal within a few minutes. 1 mL into a single nostril.
✎ 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: Duration of action is under an hour for most purposes and is shorter than that of most opioids, which is a property of the drug rather than of any particular device.
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
Naloxone has no meaningful effect in a person who has taken no opioid, which is why it can be given on suspicion. The labelled risks are all consequences of what it does rather than of toxicity: recurrent respiratory and central nervous system depression as it wears off before the opioid does; incomplete reversal of partial agonists such as buprenorphine and pentazocine; precipitation of severe opioid withdrawal in dependent patients, life-threatening in neonates if unrecognised; and adverse cardiovascular effects on abrupt postoperative reversal, chiefly in patients with pre-existing cardiovascular disease. The label states it is not a substitute for emergency medical care.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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
Intranasal spray at 2, 3, 4 and 8 mg per device; solution for intravenous, intramuscular and subcutaneous injection; a prefilled 5 mg injection; and a single-use auto-injector. Not a controlled substance; the 4 mg nasal spray has been available over the counter in the United States since March 2023.
✎ 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
1 mL into a single nostril.
✎ 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. The rest of the recorded wording: Duration of action is under an hour for most purposes and is shorter than that of most opioids, which is a property of the drug rather than of any particular device.
No source is stored against this line.
What is recorded as being sold
221 products list this as an active ingredient in the United States drug directory. 113 of them contain it and nothing else.
FDA National Drug Code directory · 72572-450 · read 2026-08-29
They are sold as film, film, soluble, inhalant, injection, injection, solution and powder, taken buccal, intramuscular, intravenous and nasal.
FDA National Drug Code directory · 72572-450 · read 2026-08-29
The regulator's established pharmacologic class for it is opioid antagonist [epc] and opioid antagonists [moa].
FDA National Drug Code directory · 72572-450 · read 2026-08-29
147 published labels name it as an active ingredient. 89 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 4951ec29-609b-4836-b0e4-0d9c1d6ae6fe · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 4951ec29-609b-4836-b0e4-0d9c1d6ae6fe · read 2026-08-29
Recorded price in US: 4.01468–13.50463 USD per one millilitre, across 27 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: 16.92243 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 5 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.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Naloxone 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 the nasal device has been shown to save lives in overdose — no trial in an overdose exists, and none could ethically be run
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 fentanyl overdose requires higher naloxone doses than standard formulations deliver, outside carfentanil exposure
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 over-the-counter status removes the barrier to access, when the price barrier documented in the pricing literature remains
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 successful reversal ends the emergency, when the label’s first warning is that depression can return as naloxone fades
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 Naloxone 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 nasal spray was approved without a trial in a single overdose
In plain words
Narcan nasal spray was licensed on two things: blood levels in healthy volunteers compared with an injection that already worked, and a study showing untrained people could operate the device. No trial ever tested it in an actual overdose, because no ethics committee could approve one.
What was measured
Plasma naloxone concentration and area under the curve for intranasal 2 to 8 mg against intramuscular 0.4 mg, and the proportion of untrained users completing both critical device tasks
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Krieter and colleagues compared the pharmacokinetics of intranasal naloxone at 2 to 8 mg delivered in 0.1 to 0.2 mL from a unit-dose device against an approved 0.4 mg intramuscular dose. All intranasal doses produced plasma concentrations and areas under the curve greater than the intramuscular dose, with no difference in time to maximum plasma concentration; concentrations were dose-proportional between 2 and 8 mg and independent of whether one or both nostrils were used. A parallel human-factors study in individuals representative of the general population found more than 90% able to perform both critical tasks — inserting the nozzle into a nostril and pressing the plunger — without prior training. On the basis of those two studies, a 4 mg single-device dose was selected as the final product. This is the correct regulatory route: an overdose cannot be randomised to placebo, and requiring an efficacy trial would mean no approved lay-administrable product at all. It remains an inference. What was measured is that the nasal device delivers more naloxone than an injection that is known to work, and that people can use it. What was not measured is a survival difference against any comparator.
Written into the record, not signed off as a reviewed claim
A generic antidote whose device price rose more than five-fold
In plain words
The molecule has been off patent since the 1980s. The auto-injector went from six hundred and ninety dollars in 2014 to four and a half thousand for a two-pack in 2016, while the epidemic it treats was accelerating.
What was measured
List price of naloxone products by year: Evzio two-pack US$690 (2014) to US$4,500 (2016); Hospira 10 mL vial US$62.29 (2012) to US$142.49 (2016)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Gupta, Shah and Ross documented the price trajectory of naloxone products in the New England Journal of Medicine in December 2016. The Evzio single-use auto-injector, fast-tracked to approval in 2014 as a fixed-dose device designed for use by people without medical training, was priced at US$690 for a two-dose package in 2014 and at US$4,500 in 2016 — an increase of more than 500% in a little over two years. Hospira’s generic injectable naloxone, the presentation carrying most of the volume, rose from US$62.29 per 10 mL vial in 2012 to US$142.49 by 2016, an increase of about 129%. The authors’ concern was structural rather than moral: naloxone is bought overwhelmingly by public health departments, harm reduction programmes and emergency services operating on fixed budgets, so a price rise translates directly into fewer kits distributed. None of these increases reflected a change in the drug. Every one attached to a delivery device layered onto a molecule that has been generic for decades — the same commercial pattern that appears on the oxycodone, hydromorphone and oxymorphone pages in this file, applied here to the antidote.
Written into the record, not signed off as a reviewed claim
The case for high-dose naloxone against fentanyl is contested
In plain words
Eight-milligram nasal sprays and five-milligram injections are sold on the idea that fentanyl needs more naloxone. A 2024 review found that most fentanyl overdoses are reversed by two standard doses, and recommended against the high-dose products on cost, withdrawal risk and lack of evidence.
What was measured
That fentanyl overdose requires higher naloxone doses than the standard formulations deliver — a premise the marketed high-dose products rest on and which this review finds unsupported outside carfentanil exposure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Lemen and colleagues reviewed the literature on whether two standard intramuscular or intranasal naloxone doses adequately reverse fentanyl overdose, incorporating the experience of a peer-led harm reduction organisation. They concluded that the evidence indicates the vast majority of fentanyl overdoses can be successfully reversed using two standard intramuscular or intranasal doses, with carfentanil the exception requiring three or more; that multiple studies document the risk of precipitated withdrawal from two or more doses, including recurrence of overdose symptoms after resuscitation depending on the half-life of the opioid involved; and that they do not recommend high-dose naloxone formulations as a substitute for four doses of standard intramuscular or intranasal naloxone, citing higher cost, risk of precipitated withdrawal and limited evidence compared with standard doses. Their recommendation is to distribute multiple standard doses to bystanders, to administer with rescue breaths at appropriate intervals until the person is revived, and to call emergency services if unresponsive after two doses. Precipitated withdrawal is the harm at issue and it is not cosmetic: a person who wakes into severe withdrawal may use again immediately, which is the outcome the extra naloxone was intended to prevent.
Written into the record, not signed off as a reviewed claim
It wears off before the opioid does, and the label says so first
In plain words
Naloxone is short-acting. Most opioids are not. Someone can be revived and then stop breathing again as it fades, which is why the first warning on the label is about surveillance rather than about dosing.
What was measured
Duration of action of naloxone relative to the opioids it reverses, as stated in the product label’s first warning
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Warning 5.1 of the naloxone nasal spray label reads: risk of recurrent respiratory and central nervous system depression — due to the duration of action of naloxone relative to the opioid, keep the patient under continued surveillance and administer repeat doses using a new nasal spray with each dose, as necessary, while awaiting emergency medical assistance. The label states in the indication itself that the product is intended for immediate administration as emergency therapy in settings where opioids may be present and is not a substitute for emergency medical care. The gap is largest for the longest-acting opioids: the methadone label reports a terminal half-life ranging from 8 to 59 hours across published studies, and extended-release formulations release for 12 to 24 hours. The mechanism is competitive antagonism — naloxone does not destroy or neutralise the opioid, it occupies the receptor while it is present, and the opioid is still in the body when it leaves.
Source
Naloxone hydrochloride nasal spray United States prescribing information, Indications 1 and Warnings and Precautions 5.1
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
Two named limits: partial agonists, and the dependent patient
In plain words
Naloxone reverses buprenorphine only partially, because buprenorphine holds the receptor too tightly. And in someone dependent on opioids it precipitates withdrawal, which in a newborn can be life-threatening.
What was measured
Labelled limits on naloxone efficacy against partial agonists and on its use in opioid-dependent patients and neonates
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Warning 5.2 states the risk of limited efficacy with partial agonists or mixed agonists and antagonists: reversal of respiratory depression caused by buprenorphine or pentazocine may be incomplete, and larger or repeated doses may be required. Warning 5.3 covers precipitation of severe opioid withdrawal in opioid-dependent patients and states that in neonates opioid withdrawal may be life-threatening if not recognised and properly treated; the same section warns that abrupt postoperative reversal of opioid depression may produce adverse cardiovascular effects, primarily in patients with pre-existing cardiovascular disorders or on other drugs with similar effects. These are the two boundaries of a competitive antagonist. Against a ligand with very slow receptor dissociation, competition is a weak lever; and in a receptor system that has adapted to constant occupancy, emptying it abruptly is itself an event.
Source
Naloxone hydrochloride nasal spray United States prescribing information, Warnings and Precautions 5.2 and 5.3
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
From prescription-only to a shelf in a convenience store
In plain words
For fifty years naloxone needed a prescription. On 29 March 2023 the FDA approved the 4 mg nasal spray for over-the-counter sale, and it can now be bought in a supermarket.
What was measured
That a prescription requirement protected patients from naloxone — a fifty-year regulatory position reversed in 2023 on the judgement that the barrier caused more harm than the drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NARCAN 4 mg nasal spray was approved under NDA 208411 and, on 29 March 2023, became the first naloxone product approved for non-prescription sale in the United States, opening distribution through pharmacies, convenience stores, supermarkets, petrol stations and online retail. A second over-the-counter naloxone nasal spray product was subsequently approved. The reversal is a regulatory one rather than a pharmacological one: nothing about the molecule changed, and the human-factors evidence that more than 90% of untrained people could operate the device had existed since the 2016 pharmacokinetic and usability programme. What changed was the judgement about where the risk lay — for decades the prescription requirement was justified as a control on a drug given to people with opioid dependence, and the conclusion shifted to the view that the barrier itself was the larger harm. It is worth noting alongside the price audit on this page: over-the-counter status removes the prescription barrier and does not remove the cost barrier.
Source
FDA approval of NARCAN (naloxone hydrochloride) nasal spray 4 mg for over-the-counter use, 29 March 2023; FDA Drugs@FDA record for NDA 208411
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
How many documents were read
79 documents were read for this substance.
RNAWiki source record
Where else this substance is registered
CAS registry number
465-65-6
PubChem compound
5284596
RxNorm concept
203192
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
✗ Not passed
Safety mode resolved
No register row and no identity class settled the question.
✓ Passed
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.
Withdrawn in United States, 2018, for "Presence of Particulate Matter; Potential for particulate matter on the syringe plunger." (openFDA drug enforcement Class I recall)
What the approval register records
122 approved applications cover products containing this substance. The earliest was NDA016636, approved 19710413 to ADAPT.
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 competitive mu-opioid antagonist that displaces the opioid from the receptor within minutes, whose approved nasal product was licensed on pharmacokinetic comparison to an intramuscular dose in healthy volunteers plus a usability study in which over 90% of untrained people performed both critical tasks — never on a randomised trial in an actual overdose, which could not ethically be run — and whose price history includes an auto-injector that went from US$690 in 2014 to US$4,500 for a two-pack in 2016.
Recorded evidence blocks (10)
Q1
On the Naloxone label: indicated for what?
"Naloxone Hydrochloride Injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids including propoxyphene, methadone, and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine.…": indications and usage on Naloxone's label. DailyMed label · 5906381c-81f4-4635-867a-e56e4d629692 · 2026-06-03
Q2
172 registered trials of Naloxone — at which phases?
Registered studies posting no result
106 of 172
172 registered studies of Naloxone: 46 phase2, 38 phase1, 37 phase4, 29 phase3, 24 na, 9 na or unstated, 7 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
1565 with a PubMed record
Show the evidence
phase2
46
phase1
38
phase4
37
phase3
29
na
24
na or unstated
9
10 more recorded rows
early phase1
7
completed
115
terminated
16
unknown
13
active not recruiting
8
recruiting
8
withdrawn
8
not yet recruiting
2
enrolling by invitation
1
suspended
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
24 of Naloxone's trials stopped: safety, accrual/recruitment, funding/business, other?
safety (1), accrual/recruitment (6), funding/business (5) and other (12): Naloxone's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
""Tapering doses" protocol arm was not effective for treatment retention outcome."; 24 of 172 registered studies
Show the evidence
Trial
NCT00552578
terminated; ""Tapering doses" protocol arm was not effective for treatment retention outcome."
NCT00678145
terminated; "Protocol was terminated due to enrollment + feasibility issues. Aim 2 not conducted. Aims 1 + 3 were conducted in part. During Aim 3 the IRB requested that the study be transitioned under a new protocol (2018-9208) in order to simplify…"
NCT00799201
terminated; "Naloxone became unavailable due to manufacturing shortatges requiring the study to be terminated."
NCT00921765
terminated; "Problems with patient recruitment"
NCT00947284
terminated; "Experimental pain model didn't work as anticipated."
NCT01015066
withdrawn; "Study personnel left institution, anticipated funding did not occur"
14 further recorded trials
NCT01841931
terminated; "Principal Investigator is no longer at this site"
NCT01851486
withdrawn; "Labortory focus was changed and study was not opened at all"
NCT01875848
terminated; "Data safety monitoring board recommended due to low recruitment yield."
NCT02700048
terminated; "research grant for the trial was not funded"
NCT03063905
terminated; "funding expired"
NCT03176316
terminated; "The study was terminated by the Institutional Review Board."
NCT03608163
terminated; "Study suspended for a prolonged duration due to the Pandemic. Once research resumed project was streamlined due to insufficient resources. Study was sufficiently powered to conduct analysis for 2 of the arms. Remaining Aims were never…"
NCT03743805
withdrawn; "Insufficient patients"
NCT03968237
withdrawn; "COVID-19 pandemic interfered with ability to conduct study."
NCT04473950
terminated; "The COVID-19 Pandemic prevented us from meeting target goals."
NCT04480554
terminated; "Funding not renewed"
NCT04737603
withdrawn; "This study was not funded and therefore not recruiting. So we never opened the study."
NCT04771689
withdrawn; "lack of funding"
NCT05114460
terminated; "The U.S. Department of Health and Human Services Office of Human Research Protections issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023. Recruitment for this trial will not…"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Naloxone used Naloxone 0.4 mg/70 kg — over how long?
Human studies of Naloxone used "Naloxone 0.4 mg/70 kg". ClinicalTrials.gov · 2026-09-01
12 recorded entries; human; nasal, sublingual; also "Naloxone 0.8 mg/70 kg", "2.0mg Buprenorphine/0.5mg Naloxone", "Naloxone (2 mg/kg)"
Show the evidence
human
NCT01549652
Naloxone 0.4 mg/70 kg
NCT01549652
Naloxone 0.8 mg/70 kg
NCT01846455
2.0mg Buprenorphine/0.5mg Naloxone
NCT01935206
Naloxone (2 mg/kg)
NCT02137213
Naloxone hydrochloride solution for injections 0.4 mg/ml
NCT02267304
Naloxone 10mg
6 more recorded rows
humanNCT03430180
nasal; Naloxone 40mg/ml nasal spray when craving to gamble
humanNCT05301712
Naloxone hydrochloride 5.0mg/5ml
humanNCT05338632
Narcan 40 MG/ML Nasal Spray
humanNCT06251609
Naloxone 2 MG
humanNCT07439549
Naloxone Hydrochloride 0.4 MG/ML
humanNCT07439549
sublingual; Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg)
recorded 2026-09-01 · last checked 2026-09-04
Q5
Naloxone's half-life is 30 to 81 minutes — which schedules were studied?
30 to 81 minutes; In one study, the serum half-life in adults ranged from 30 to 81 minutes (mean 64 ± 12 minutes).
metabolismpharmacokinetics
Metabolism and Elimination Naloxone is metabolized in the liver primarily by glucuronide conjugation with naloxone-3-glucuronide as the major metabolite.
recorded 2026-06-03 · last checked 2026-09-04
Q6
Which running trial of Naloxone could settle lifespan?
NCT06251609 measures Survival to hospital discharge, reading out 2028-12-31.
1 open trial; n 98; "Naloxone for Opioid Associated Out of Hospital Cardiac Arrest"
Show the evidence
TrialNCT06251609
"Naloxone for Opioid Associated Out of Hospital Cardiac Arrest"; n 98; "Survival to hospital discharge"; 2028-12-31
Q7
Which 54 trials of Naloxone posted no result?
Posted no result
54 of 54 completed trials
Registrations
NCT00000320, NCT00007527, NCT01367561, NCT00142896, NCT00108446 and NCT00367302, and 48 more
Completion dates
oldest 1999-08; newest 2023-12-27
Show the evidence
Trial
NCT00000320
1999-08
NCT00007527
2002-01
NCT01367561
2003-05
NCT00142896
2005-12
NCT00108446
2006-03
NCT00367302
2008-01
14 further recorded trials
NCT00733720
2009-01
NCT00829777
2009-09
NCT00901875
2010-01
NCT00593463
2010-05
NCT00890942
2010-05
NCT01191645
2010-11
NCT01260675
2011-01-31
NCT00955162
2011-05
NCT01114308
2011-05
NCT01109511
2011-07-30
NCT01596764
2012-01
NCT01591629
2012-06-01
NCT01582347
2012-11
NCT00877591
2013-04
Q8
At the median, Naloxone's trials enrolled 50 people — anything larger?
Median enrolment
50
Largest enrolment
6000
Registered trials counted
170
Q9
What do 2735 spontaneous reports say about Naloxone — 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.
Naloxone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2735 reaction mentions were counted: nausea 513; drug withdrawal syndrome 494; vomiting 408; drug dependence 262. FAERS via Open Targets · CHEMBL1718 · 2026-06-24
Show the evidence
nausea
513
drug withdrawal syndrome
494
vomiting
408
drug dependence
262
drug abuse
259
drug withdrawal syndrome neonatal
220
4 more recorded rows
wrong technique in product usage process
185
hyperhidrosis
143
substance abuse
130
stomatitis
121
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Naloxone's label not list?
3 label terms; 10 reported and unlisted; 5906381c-81f4-4635-867a-e56e4d629692
Show the evidence
drug abuse
count not stated
drug dependence
count not stated
drug withdrawal syndrome
count not stated
drug withdrawal syndrome neonatal
count not stated
hyperhidrosis
count not stated
nausea
count not stated
4 more recorded rows
stomatitis
count not stated
substance abuse
count not stated
vomiting
count not stated
wrong technique in product usage process
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Where it is registered
Where it’s registered
Withdrawn in United States, 2018, for "Presence of Particulate Matter; Potential for particulate matter on the syringe plunger." (openFDA drug enforcement Class I recall)
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 · openFDA enforcement — 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: 7 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.