This page shows what was measured, who it was measured in, and what that does not settle.
What Xylazine does in the body
Activating it turns down sympathetic nervous system output: sedation, slow heart rate, low blood pressure.
Xylazine works on the alpha-2 adrenergic receptor, the same target as clonidine, which is a blood-pressure drug. None of that involves an opioid receptor, so naloxone — which works by competing with opioids at their receptor — has nothing to compete with. In an overdose where both fentanyl and xylazine are present, naloxone restores breathing driven by the opioid and leaves the xylazine sedation untouched. That is the whole clinical story, and it is why supportive care rather than an antidote is the recommendation.
Why people take it. A veterinary tranquilliser increasingly mixed into illicit fentanyl.
What happened in people
Across 21 areas, its share of fentanyl-related deaths rose from under 3 in 100 to nearly 11.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Regional comparisons are distorted because many places do not routinely test for xylazine.
Where it acts
Presynaptic alpha-2 adrenoceptors in the brainstem and spinal cord, reducing sympathetic outflow — producing sedation, bradycardia and hypotension by a mechanism entirely separate from any opioid
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 2KFG9TP5V8 · read 2026-08-29
Its recorded molecular formula is C12H16N2S, weighing 220.34.
PubChem record · 5707 · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 122 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.
Protein
A protein is a folded chain your body builds to do a specific job.
A picture of it, and where the picture fails
A protein is like a tool bent into one shape for one task.
Where that stops being true. A tool keeps its shape. A protein can change shape and stop working.
What people get wrong. Protein in food and a protein in the body are related but not the same thing.
A polymer of amino acids folded into a defined structure that determines its function.
Enzyme
An enzyme is a protein that speeds up one chemical change.
A picture of it, and where the picture fails
An enzyme is like a machine on a production line doing one cut.
Where that stops being true. A machine is switched on and off by a person. Enzymes are controlled by the cell.
What people get wrong. Enzymes are thought to be used up. They are not; they work again and again.
A catalytic protein that lowers the activation energy of a specific reaction.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
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.
Monthly percentage of illicitly-manufactured-fentanyl-involved overdose deaths with xylazine detected
✓ The study showed what it set out to show
Who was studied
Kariisa et al. 2023 SUDORS analysis, January 2019-June 2022
How many people
0
Study design
National surveillance analysis
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Increase of 276%, from 2.9% to 10.9%, across 21 jurisdictions over the study period
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. Detection depends on the jurisdiction testing for xylazine, and whether a detected result was listed as a cause of death varied between jurisdictions. The regional gradient partly reflects testing practice.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injected or inhaled as an adulterant within illicit opioid powder
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Trend and geographic distribution of xylazine-present overdose mortality across the United States
✓ The study showed what it set out to show
Who was studied
Friedman et al. 2022 mixed-methods national assessment
How many people
0
Study design
Sequential mixed-methods surveillance and ethnography
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Rose from 0.36% of deaths in 2015 to 6.7% in 2020 across 10 jurisdictions; Philadelphia 25.8%, Maryland 19.3%, Connecticut 10.2%; IMF co-present in 98.4%
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. Many jurisdictions do not routinely test for xylazine and it is not comprehensively tracked nationally, so all percentages are floors. The ethnographic component is qualitative and not quantifiable.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injected or inhaled as an adulterant within illicit opioid powder
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Management of xylazine toxicity, overdose, dependence and withdrawal in humans
✗ The study did not show it
Who was studied
Owusu-Antwi et al. 2025 systematic review of human xylazine management
How many people
34
Study design
PRISMA systematic review, 1957-2024
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Doses 40 mg to 4,300 mg with no established toxic dosing; no antidote and no evidence-based treatment recommendations identified
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. Sixty-seven years of literature yielded 34 studies and no controlled trial. Misuse was almost always alongside other substances, so effects cannot be attributed to xylazine alone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Injected or inhaled as an adulterant within illicit opioid powder
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
□A step measured inside a personNo evidence recorded. Something measured in human tissue or human cells.No registered study measures this.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
□Cells in a dishNo evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the 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
Xylazine
What a person takes: Injected or inhaled as an adulterant within illicit opioid powder.
The measurement behind this step
There is no human delivery system, because there is no human product. Xylazine reaches people mixed into powder sold as fentanyl or heroin, at concentrations nobody has measured before use. The veterinary product is an injectable solution intended for large animals, and its diversion route into the illicit supply is not through the prescription system, because none exists for it in humans.
Getting in
Added to the fentanyl, usually before the buyer sees it
It arrives mixed into powder sold as fentanyl or heroin. Some people now seek it out, because it makes a short fentanyl effect last longer.
╌╌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
Present in 98.4% of xylazine-positive overdose deaths alongside illicitly manufactured fentanyls. Philadelphia ethnography records a demand that developed after the exposure did: users describe it as lengthening the short duration of a fentanyl injection.
Injected or inhaled with the opioid, it reaches the brain on the same timescale.
──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
Small lipophilic molecule, 220.34 g/mol, with rapid central distribution. Reported human doses span 40 mg to 4,300 mg with no established toxic dose, so exposure cannot be characterised from the amount taken.
The same receptor clonidine works on. Activating it reduces sympathetic nervous system output — sedation, slow pulse, low blood pressure.
╌╌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
Alpha-2 adrenoceptor agonism, in the same pharmacological class as clonidine and dexmedetomidine, producing central nervous system depression, respiratory depression, bradycardia and hypotension in humans. No opioid receptor activity whatsoever.
Naloxone reverses the fentanyl and does nothing to the xylazine. The person may resume breathing and stay deeply sedated.
╌╌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
Naloxone is a competitive µ-opioid antagonist and has no mechanism against an alpha-2 agonist. CDC therefore recommends respiratory and cardiovascular support alongside naloxone. Alpha-2 antagonists reverse xylazine in animals; none is approved for this indication in people.
Chronic use is associated with deep skin ulcers, sometimes at sites where the person never injected, and with a severe withdrawal syndrome.
╌╌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
Severe withdrawal symptoms and skin ulcerations are both documented with chronic use. The wound mechanism is unestablished; peripheral vasoconstriction from alpha-2 agonism is the usual proposal. There is no antidote and no evidence-based treatment recommendation for any of it.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or 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.
Almost nobody deliberately, at first. People who inject drugs in Philadelphia described it to ethnographers as a sought-after adulterant that lengthens the short duration of a fentanyl injection, so a deliberate demand has developed downstream of an involuntary exposure.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
Xylazine entered and spread through the US illicit supply without triggering any control mechanism, because it is a veterinary product rather than a scheduled or novel psychoactive substance
No controlled human study of xylazine exists, and the systematic review searching from 1957 found none
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
Varies by country
❝ 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
Injected or inhaled as an adulterant within illicit opioid powder
✎ 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
There is no human delivery system, because there is no human product. Xylazine reaches people mixed into powder sold as fentanyl or heroin, at concentrations nobody has measured before use.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The veterinary product is an injectable solution intended for large animals, and its diversion route into the illicit supply is not through the prescription system, because none exists for it in humans.
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
Documented effects in humans are central nervous system depression, respiratory depression, bradycardia and hypotension. There is no antidote: naloxone reverses the opioid component and leaves the xylazine sedation, so management is respiratory and cardiovascular support. Chronic exposure is associated with severe skin ulceration, including at sites distant from injection, and with a severe withdrawal syndrome for which no evidence-based regimen exists. Reported doses in the human literature span two orders of magnitude with no established toxic threshold. Because it is almost always co-present with illicitly manufactured fentanyl, and frequently with cocaine, benzodiazepine-type compounds and alcohol, no clinical presentation in this literature is attributable to xylazine alone.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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.
Xylazine appears in spontaneous reports to regulators. Across the 2 most-reported reaction terms, 12 reaction mentions were counted. One report can name several reactions.
The recorded terms (2)
toxicity to various agents — 7 reaction mentions
substance use — 5 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or 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
Injected or inhaled as an adulterant within illicit opioid powder
✎ 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
Xylazine reaches people mixed into powder sold as fentanyl or heroin, at concentrations nobody has measured before use.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold. The rest of the recorded wording: The veterinary product is an injectable solution intended for large animals, and its diversion route into the illicit supply is not through the prescription system, because none exists for it in humans.
No source is stored against this line.
What is recorded as being sold
5 products list this as an active ingredient in the United States drug directory. 5 of them contain it and nothing else.
FDA National Drug Code directory · 54871-1099 · read 2026-08-29
They are sold as injection and powder.
FDA National Drug Code directory · 54871-1099 · read 2026-08-29
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 Xylazine 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 regional differences in detected xylazine describe differences in exposure rather than in testing practice
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 naloxone should be withheld or reduced because it will not reverse xylazine — the opioid component is almost always present and is reversible
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 alpha-2-mediated vasoconstriction is the established cause of the ulcers; it is the leading proposal and has not been demonstrated
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 xylazine concentration in a death investigation attributes causation, when fentanyl is co-present in nearly every case
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Xylazine 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.
From 2.9% to 10.9% of fentanyl deaths in three and a half years
In plain words
CDC tracked overdose deaths involving illicitly made fentanyl across 21 jurisdictions. The monthly share with xylazine also detected rose 276%, from under 3% to nearly 11%.
What was measured
Monthly percentage of IMF-involved overdose deaths with xylazine detected, 21 jurisdictions, January 2019-June 2022
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Kariisa et al. used CDC's State Unintentional Drug Overdose Reporting System to describe illicitly-manufactured-fentanyl-involved overdose deaths with and without detected xylazine from January 2019 to June 2022. Across 21 jurisdictions — 20 states and the District of Columbia — the monthly percentage of IMF-involved deaths with xylazine detected rose 276%, from 2.9% to 10.9%. Across 32 jurisdictions for January 2021 to June 2022, xylazine was detected in a higher percentage of jurisdictions in the Northeast Census region, and whether detected xylazine was listed as a cause of death varied across jurisdictions. In 2022, provisional data recorded 107,081 drug overdose deaths in the United States, more than two thirds involving synthetic opioids other than methadone. The authors call for expanded postmortem and drug-product testing to clarify prevalence, and for overdose response messages to emphasise respiratory and cardiovascular support because there is no antidote.
Written into the record, not signed off as a reviewed claim
Almost always with fentanyl: 98.4% co-detection
In plain words
Across ten jurisdictions spanning all four US regions, xylazine rose from 0.36% of overdose deaths in 2015 to 6.7% in 2020. Illicit fentanyl was present in 98.4% of the xylazine cases.
What was measured
Percentage of overdose deaths with xylazine present by jurisdiction and year, with co-detected substance frequencies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Friedman et al. combined ethnographic observation in Philadelphia with a systematic search for records of xylazine-present overdose mortality across the United States. In 10 jurisdictions representing all four Census regions, xylazine rose from 0.36% of overdose deaths in 2015 to 6.7% in 2020. Prevalence was highest in Philadelphia at 25.8% of deaths, then Maryland at 19.3% and Connecticut at 10.2%. Illicitly manufactured fentanyls were present in 98.4% of xylazine-present overdose deaths, alongside cocaine in 45.4%, benzodiazepines in 28.4%, heroin in 23.3% and alcohol in 19.7%. People who inject drugs in Philadelphia described xylazine as a sought-after adulterant that lengthens the short duration of a fentanyl injection, and linked it to increased soft-tissue infection and to naloxone-resistant overdose. The authors note that many jurisdictions do not routinely test for xylazine and that it is not comprehensively tracked nationally — so these figures are floors, not estimates.
Written into the record, not signed off as a reviewed claim
Naloxone does not reverse it, because there is nothing for it to compete with
In plain words
Xylazine acts on the adrenaline system, not the opioid system. Naloxone works by displacing opioids from their receptor, so it has no effect on xylazine sedation at all.
What was measured
Receptor class of xylazine against the mechanism of naloxone, with the clinical management recommendation that follows
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Xylazine is an alpha-2 adrenergic receptor agonist with no opioid receptor activity. Naloxone is a competitive antagonist at the µ-opioid receptor and reverses opioid effects by displacing the agonist; it has no mechanism of action against an alpha-2 agonist. CDC describes xylazine as "a nonopioid sedative not approved for human use and with no known antidote", and states that limited studies show it can cause central nervous system depression, respiratory depression, bradycardia and hypotension in humans. The clinical implication CDC draws is specific: overdose response messaging must emphasise respiratory and cardiovascular support to address the sedative effects, in addition to naloxone for the opioid component. The corollary matters as much: naloxone should still be given, because the opioid component is almost always present and is reversible — a partial response is not a reason to withhold it.
Written into the record, not signed off as a reviewed claim
Systematic review: no antidote, no toxic dose, no evidence-based treatment
In plain words
A review of every human study from 1957 to 2024 found 34 papers. Reported doses ranged from 40 mg to 4,300 mg, no toxic dose has ever been established, and there is no antidote or evidence-based treatment guidance.
What was measured
Number of included human studies, reported dose range, and availability of an antidote or evidence-based treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Owusu-Antwi et al. searched the literature from 1957 to 2024 under PRISMA guidance with JBI critical appraisal, including 34 studies on management of xylazine intoxication, withdrawal, overdose and dependence in humans. Misuse was commonest among men aged 19 to 45 and was more likely to occur with other substances than alone. Reported doses ranged from 40 mg to 4,300 mg, with no established toxic dosing. Supportive care described in the literature included naloxone, alpha-2 agonists and GABAergic medications. The review's conclusion is a null one and is the most important sentence in it: there is no antidote and no evidence-based treatment recommendation. Sixty-seven years of literature on a compound now present in a tenth of American fentanyl deaths amounts to 34 papers, none of them a controlled trial.
Written into the record, not signed off as a reviewed claim
A veterinary drug in the human drug supply, and in no drug schedule
In plain words
Xylazine is an approved animal medicine that appears nowhere in the federal drug schedules. It became a major feature of the US overdose crisis without ever being a controlled substance.
What was measured
Regulatory status of xylazine against its measured prevalence in overdose deaths
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Xylazine holds veterinary approvals as a sedative, analgesic and muscle relaxant, has never had a human application submitted in the United States, and appears in no schedule of 21 CFR part 1308. Its arrival in the illicit supply therefore happened entirely outside the framework built to track and control such arrivals: it is not a novel psychoactive substance requiring analogue analysis, not a diverted prescription medicine, and not a scheduled drug whose movement can be monitored through the registrant system. Long noted in the Puerto Rico street opioid supply and later Philadelphia, it spread nationally between 2015 and 2020 while, as Friedman et al. put it, many jurisdictions did not routinely test for it and it was not comprehensively tracked nationally. The record here is a category failure rather than a scientific one: a substance with no human indication became a leading adulterant because nothing in the regulatory architecture was pointed at it.
Written into the record, not signed off as a reviewed claim
Severe skin ulceration, at sites unrelated to injection
In plain words
Chronic xylazine exposure is associated with deep, slow-healing skin ulcers, including on parts of the body where the person did not inject.
What was measured
Documented association between chronic xylazine exposure and severe skin ulceration and soft-tissue infection
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CDC states that chronic use might lead to severe withdrawal symptoms as well as skin ulcerations, and the Philadelphia ethnographic work links xylazine to increased risk of soft-tissue infection. The wounds described in the clinical literature are necrotic ulcers that may appear at sites distant from injection, which distinguishes them from ordinary injection-site abscess and points to a systemic rather than a local mechanism; peripheral vasoconstriction from alpha-2 agonism is the usual proposed explanation and has not been demonstrated as the cause. This record files the association as measured — the ulcers are documented and their link to xylazine exposure is consistent across sources — while noting that the mechanism is not established and that people with this exposure also have multiple other risks for poor wound healing.
Written into the record, not signed off as a reviewed claim
Prevalence figures measure testing, not exposure
In plain words
Xylazine looks commonest in the Northeast. That may partly be because the Northeast tests for it most, and many jurisdictions do not test at all.
What was measured
That measured regional and temporal differences in xylazine detection describe differences in exposure rather than differences in testing practice
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both major surveillance sources state the limitation directly. Friedman et al. note that many jurisdictions do not routinely test for xylazine and that it is not comprehensively tracked nationally. Kariisa et al. report that xylazine was detected in a higher percentage of jurisdictions in the Northeast and that whether detected xylazine was listed as a cause of death varied across jurisdictions, and call for expanded postmortem and illicit-drug-product testing to clarify prevalence. A geographic gradient in a substance that is only found where it is looked for is therefore uninterpretable as a gradient in exposure, and every published percentage in this record should be read as a floor. This is the same inference problem as the kratom postmortem series, and it applies wherever detection depends on a jurisdiction having chosen to add an analyte.
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What is not here
6 questions this page could not answer
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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
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A veterinary alpha-2 agonist with no human approval and no place in any federal drug schedule, present in 25.8% of Philadelphia overdose deaths by 2020 and in 98.4% of cases alongside illicitly manufactured fentanyl — and naloxone does not reverse it, because it is not an opioid.
2 of 8 rungs carry a finding; no outcome wording is recorded.
Show the evidence
mouse
lifespan
rat
mechanism-only
recorded 2026-05-28 · last checked 2026-09-04
Q3
What do 12 spontaneous reports say about Xylazine — 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.
Xylazine appears in spontaneous reports to regulators. Across the 2 most-reported reaction terms, 12 reaction mentions were counted: toxicity to various agents 7; substance use 5. open-targets-adr · CHEMBL297362 · 2026-06-24
Show the evidence
toxicity to various agents
7
substance use
5
recorded 2026-06-24 · last checked 2026-09-04
Q4
Was Xylazine studied with fasting?
fasting is named in Xylazine's label sentences: "Following overnight fasting, the 10-week trial was concluded with intramuscular injections of anesthetic drugs xylazine (8-10 mg/kg) and ketamine (80-100 mg/kg), and subsequently, the collection of cardiac blood." openfda-label+europepmc · 2024-10-30
1 recorded statement; fasting
Show the evidence
fasting
Following overnight fasting, the 10-week trial was concluded with intramuscular injections of anesthetic drugs xylazine (8-10 mg/kg) and ketamine (80-100 mg/kg), and subsequently, the collection of cardiac blood.
recorded 2024-10-30 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
Xylazine component of tranq, Rompun, AnaSed, Sedazine and other veterinary products. In the illicit supply it is known as "tranq" and appears as an adulterant rather than a named product
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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