This page shows what was measured, who it was measured in, and what that does not settle.
What Diphenhydramine does in the body
Allergic reactions, itching, motion sickness and short-term sleep problems.
Histamine sits in the receptor and starts the allergic reaction; this drug takes the seat first and holds it. What separates it from the modern antihistamines is that it does not stay where the allergy is. It crosses into the brain, where histamine is one of the signals that keeps you awake, and blocking it there is what makes you drowsy. It also blocks a second, unrelated receptor for acetylcholine, which is why it dries your mouth and eyes, blurs vision, slows the gut and can make an older person confused.
What happened in people
In a driving simulator, it impaired driving more than alcohol near the legal limit.
✓ 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
Long-term dementia findings come from population associations and do not prove this drug caused dementia.
Where it acts
Everywhere — peripheral H1 receptors in nose and skin, brain H1 receptors in the tuberomammillary wakefulness pathway, and muscarinic receptors in bladder, gut, eye and cortex
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 116 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Pain
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer2 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Energy
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Recovery
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Pain
pain intensity; pain tolerance
Energy
energy expenditure
Recovery
time for recovery
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
2 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
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.
Coherence — ability to match the varying speed of a lead vehicle over one hour of simulated driving
✗ The study did not show it
Who was studied
Weiler 2000 (Iowa Driving Simulator, Ann Intern Med 132:354-363)
Coherence significantly worse after diphenhydramine 50 mg than after alcohol at approximately 0.1% blood alcohol concentration or after fexofenadine; lane keeping impaired relative to fexofenadine
Repeated elsewhere
Replicated
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. Self-reported drowsiness did not predict lack of coherence, so subjects were impaired without being able to detect it.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Significantly greater sleepiness and impairment than placebo on day 1; indistinguishable from placebo by day 4
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. Fifteen healthy young men, four days. Tolerance to the antimuscarinic effects was not assessed and there is no evidence it develops on the same schedule.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Parental report of improvement in night awakenings requiring assistance at day 14, in infants aged 6 to 15 months
✗ The study did not show it
Who was studied
TIRED (Arch Pediatr Adolesc Med 2006;160:707-712)
How many people
44
Study design
Randomised, double-blind, placebo-controlled — stopped early for futility
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
1 of 22 improved on diphenhydramine against 3 of 22 on placebo; data safety monitoring board voted unanimously to stop for lack of effectiveness
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. Stopped at 44 of a planned larger enrolment, so the trial is small. The direction of the result and the futility calculation are nonetheless unambiguous.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Two-hour change from baseline in patient-rated pruritus score in acute urticaria
✓ The study showed what it set out to show
Who was studied
Abella 2020 (Ann Emerg Med 76:489-500)
How many people
262
Study design
Phase 3, multicentre, randomised, noninferiority — as the active comparator
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Intravenous cetirizine -1.6 against intravenous diphenhydramine -1.5 (95% CI -0.1 to 0.3), noninferiority met in cetirizine’s favour
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Diphenhydramine patients spent longer in the treatment centre (2.1 against 1.7 hours, p=0.005), returned more often (14.1% against 5.5%, p=0.02) and were more sedated (0.5 against 0.1, p=0.03). The trial was designed and funded to displace it.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
Incident dementia and Alzheimer disease against ten-year cumulative anticholinergic exposure
✓ The study showed what it set out to show
Who was studied
Adult Changes in Thought cohort (JAMA Intern Med 2015;175:401-407)
How many people
3434
Study design
Prospective population-based cohort, not a trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Dose-response trend p<0.001; adjusted hazard ratio 1.54 (95% CI 1.21 to 1.96) above 1,095 total standardised daily doses against non-use
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Observational. Exposure is measured across a whole anticholinergic class rather than for diphenhydramine specifically, and confounding by indication cannot be excluded.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 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 eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.5 registered measures of this kind. No reviewed result.
■What a body can do day to dayEvidence recorded. Walking, dressing, breathing, recovering.1 registered measure of this kind.
■Measured performanceEvidence recorded. How much was lifted, how far was run, how fast.1 registered measure of this kind.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.2 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.1 registered measure of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Rat. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□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
Diphenhydramine
What a person takes: Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States.
The measurement behind this step
The injectable form is labelled for use when oral therapy is impossible or contraindicated. Onset of sedation after an oral dose is within about an hour; the effect on driving is present at that point whether or not the person feels it.
Getting in
Absorbed quickly and heavily processed by the liver
It gets into the blood fast, which is why drowsiness arrives within an hour. A large fraction is broken down by the liver before it ever reaches the circulation.
──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
A small, lipophilic tertiary amine with high oral absorption and extensive first-pass metabolism, principally by CYP2D6 with contributions from CYP1A2, CYP2C9 and CYP2C19. Poor CYP2D6 metabolisers reach substantially higher exposure from the same amount. Elimination half-life lengthens in older adults, which compounds the sensitivity that age already brings.
Nothing in the molecule stops it entering the brain. That is not a flaw in the design; the design predates the idea that an antihistamine should stay out.
╌╌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
The molecule is uncharged apart from a single basic amine, has no carboxylate to form a zwitterion and is not a strong P-glycoprotein substrate, so it distributes freely across the blood-brain barrier. Brain H1 receptor occupancy for first-generation antihistamines measured by PET runs to a large fraction of available receptors, against -0.1% for fexofenadine in the same kind of study.
It blocks the histamine receptor in two places at once
In the nose and skin, blocking the receptor stops the allergic itching and running. In the brain, the same receptor is part of the system that keeps you awake, and blocking it there makes you sleepy. The drug cannot separate the two.
╌╌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
Peripheral HRH1 antagonism on postcapillary venule endothelium and sensory nerve endings produces the antiallergic effect. Central HRH1 antagonism in the projections of the tuberomammillary nucleus suppresses histaminergic arousal, producing sedation. The therapeutic effect and the principal adverse effect are the same molecular event in two tissues.
Alongside histamine, it blocks the receptor for acetylcholine. That is what dries the mouth and eyes, blurs near vision, slows the bowel, makes passing urine harder and can tip an older person into confusion.
╌╌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
Muscarinic acetylcholine receptor antagonism is substantial rather than incidental, and the H1-to-muscarinic selectivity ratio is close enough to one that ordinary doses produce measurable antimuscarinic effects. This is why the drug appears on the American Geriatrics Society Beers Criteria and why it dominates the anticholinergic-burden scales used in geriatric practice.
Take it every night and within four days you no longer feel drowsy from it. The dry mouth, the blurred vision and the effect on the bladder and bowel carry on.
╌╌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
Objective and subjective sleepiness on 50 mg twice daily were significantly above placebo on day 1 and indistinguishable from placebo by day 4 in a randomised crossover, with psychomotor impairment reversing on the same schedule. No comparable tolerance to antimuscarinic effects has been demonstrated, so continued use shifts the balance of effects unfavourably over days.
Taken in large amounts it produces agitation, hallucinations, fever, a racing heart and seizures. It is one of the drugs poison centres see most often in deliberate overdose, precisely because it is cheap and unrestricted.
╌╌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
Massive ingestion produces the full anticholinergic toxidrome together with cardiac complications and seizures. In a National Poison Data System series of 24,358 paediatric and adolescent cases, ingestions of 2,500 mg or more led to inpatient admission in 69.6% of cases and to major effects — life-threatening symptoms, residual disability or death — in 21.3%, against 1.0% for smaller ingestions.
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 it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
pain intensity
pain tolerance
Measured
Things only a test, a scale or a device shows.
cmax in plasma of naproxen sodium
Meaningful
Things that change how a life goes, not only a number.
relapse free complete clinical response
progression free survival in advanced stage dlbcl
event free survival per protocol
overall survival at 2 years and 5 years
distance walked during a six minute walk test
progression free survival
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (31)
response rate
acute rejections in all enrolled
chronic graft vs host disease
dose limiting toxicity number of dlts by treatment group
dose limiting toxicity number of affected
at least 1 serious adverse event
clinical response rate
tramadol er reduces vas for oih
likert scale for satisfaction
pharmacokinetic parameters
urticaria activity 7 from baseline to week 4
bmi z
incidence of graft versus host disease
toxicity
resting metabolic rate
food intake
energy expenditure
average percentage of sedation failures
time for recovery
physical activity
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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.
Adults and children, over the counter, for allergy, for itch, for travel sickness and for sleep. It is also the only intravenous antihistamine that was available in the United States for sixty-four years.
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: “Diphenhydramine should not be used in neonates and premature infants (see CONTRAINDICATIONS ).”
US prescribing information · 5bbbd6e5-4d0a-4380-bbd3-3313ff26cda0 · read 2026-08-30
On people who are pregnant, the label states: “Teratogenic Effects Reproduction studies have been performed in rats and rabbits at doses up to 5 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to diphenhydramine hydrochloride.”
US prescribing information · 5bbbd6e5-4d0a-4380-bbd3-3313ff26cda0 · read 2026-08-30
Where the result stopped carrying
TIRED was stopped by its data safety monitoring board for lack of effectiveness in infant night waking
The sedative effect, which is the reason it is bought as a sleep aid, disappears within four days of continuous use
The American Academy of Sleep Medicine reviewed the randomised evidence and recommended against using it for insomnia in adults
In the emergency department trial it lost on sedation, on length of stay and on repeat presentations while merely matching on itch relief
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 for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.
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 (9)
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
Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
The injectable form is labelled for use when oral therapy is impossible or contraindicated. Onset of sedation after an oral dose is within about an hour; the effect on driving is present at that point whether or not the person feels it.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to 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
Sedation and psychomotor impairment exceeding that produced by alcohol at roughly the legal driving limit, with tolerance to the sedation but not to the rest within four days. A full antimuscarinic profile at ordinary doses: dry mouth, blurred near vision, constipation, urinary retention and, in older adults, confusion. Paradoxical excitation is common in young children, and fatal monointoxication in infants is documented. In massive ingestion the anticholinergic toxidrome is accompanied by cardiac complications and seizures. Metabolised by CYP2D6, so poor metabolisers and people taking CYP2D6 inhibitors reach higher exposure.
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.
Diphenhydramine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1807 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
drug hypersensitivity — 414 reaction mentions
nausea — 245 reaction mentions
headache — 220 reaction mentions
vomiting — 154 reaction mentions
dizziness — 151 reaction mentions
decreased appetite — 146 reaction mentions
weight decreased — 124 reaction mentions
pharyngitis — 120 reaction mentions
ear infection — 119 reaction mentions
abdominal discomfort — 114 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
Oral tablet, capsule, liquid and orally disintegrating strip; topical cream; and injection, which for sixty-four years was the only intravenous antihistamine available in the United States
✎ 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
Onset of sedation after an oral dose is within about an hour; the effect on driving is present at that point whether or not the person feels it.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
1231 products list this as an active ingredient in the United States drug directory. 811 of them contain it and nothing else.
FDA National Drug Code directory · 71399-1028 · read 2026-08-29
They are sold as aerosol, spray, bar, chewable, capsule, capsule, coated, capsule, gelatin coated and capsule, liquid filled, taken cutaneous, intramuscular, intravenous and oral.
FDA National Drug Code directory · 71399-1028 · read 2026-08-29
The regulator's established pharmacologic class for it is histamine h1 receptor antagonists [moa] and histamine-1 receptor antagonist [epc].
FDA National Drug Code directory · 71399-1028 · read 2026-08-29
1104 published labels name it as an active ingredient. 726 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 9819522f-f3db-4cb8-9680-423114ace2f6 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 9819522f-f3db-4cb8-9680-423114ace2f6 · read 2026-08-29
Diphenhydramine is intramuscular at HOW SUPPLIED Diphenhydramine Hydrochloride Injection, USP 50 mg per mL is a clear, colorless solution supplied as follows: NDC Diphenhydramine Hydrochloride Injection, USP Package Factor 83634-781-01 50 mg per mL Single…, recorded as fda label in effect 2025-05-16 in the United States.
US prescribing information · 00f862aa-6917-45c7-b6aa-1bebb0a45e14 · read 2026-09-12
Recorded price in US: 0.01751–1.01048 USD per one millilitre, across 16 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Recorded price in US: 0.03131–0.05416 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 8 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.
Evidence on this page does not automatically apply to this one.
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 Diphenhydramine 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 being the only active ingredient in the over-the-counter nighttime sleep-aid monograph means it has been shown to treat insomnia
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 eighty years on the market constitutes evidence of effectiveness — the drug predates the 1962 requirement to prove any
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the cumulative anticholinergic dementia association proves causation, when it is an observational class-level exposure measure
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 feeling alert on it means driving is unaffected — self-reported drowsiness failed to predict measured impairment
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 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 Diphenhydramine 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.
It impaired driving more than being over the drink-drive limit
In plain words
Forty licensed drivers drove for an hour in a simulator on four separate weeks: on this drug, on a modern antihistamine, on enough alcohol to put them around the legal limit, and on a dummy tablet. This drug was the worst of the four.
What was measured
Coherence, steering instability and centre-line crossings over one hour of simulated driving
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In a randomised, double-blind, double-dummy four-period crossover in the Iowa Driving Simulator, 40 licensed drivers aged 25 to 44 with seasonal allergic rhinitis received diphenhydramine 50 mg, fexofenadine 60 mg, alcohol to approximately 0.1% blood alcohol concentration, or placebo at weekly intervals. Coherence — the ability to match a lead vehicle’s varying speed — was significantly better after alcohol or fexofenadine than after diphenhydramine. Lane keeping, measured as steering instability and centre-line crossings, was impaired after both alcohol and diphenhydramine relative to fexofenadine. Self-reported drowsiness did not predict lack of coherence, so subjects could not tell how impaired they were.
Written into the record, not signed off as a reviewed claim
The sedative effect is completely gone by the fourth night
In plain words
The reason people take this for sleep is that it makes them drowsy. Measured objectively, that drowsiness disappears within four days of taking it every day. The drying and the other effects do not disappear.
What was measured
Objective and subjective sleepiness and psychomotor performance, day 1 against day 4 of continuous dosing
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Fifteen healthy men aged 18 to 50 received diphenhydramine 50 mg or placebo twice daily for four days in a randomised, double-blind crossover, with objective and subjective sleepiness measures and computer-based psychomotor testing. Both objective and subjective sleepiness were significantly higher on diphenhydramine than placebo on day 1. By day 4, sleepiness on diphenhydramine was indistinguishable from placebo, and the significant psychomotor impairment seen initially had completely reversed. The authors described this as the first objective demonstration of tolerance to the sedative effect of a first-generation H1 antihistamine.
Written into the record, not signed off as a reviewed claim
TIRED: it did not settle infants, and a safety board stopped the trial
In plain words
A randomised trial gave this drug or a placebo to infants who woke frequently at night. It was stopped early because the drug was doing nothing. One infant of twenty-two improved on the drug; three of twenty-two improved on placebo.
What was measured
Parental report of improvement in night awakenings requiring assistance, day 14
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Trial of Infant Response to Diphenhydramine was a double-blind, randomised, controlled trial in 44 infants aged 6 to 15 months with frequent parent-reported night awakenings, dosed 30 minutes before anticipated bedtime for one week with follow-up at 2 and 4 weeks. On 6 June 2005 the data safety monitoring board voted unanimously to stop the trial early for lack of effectiveness. One of 22 children on diphenhydramine improved against 3 of 22 on placebo. The authors calculated that to reach the pre-specified sample size and still reject the null hypothesis, 15 of the next 16 diphenhydramine infants and none of the next 16 placebo infants would have had to improve.
Written into the record, not signed off as a reviewed claim
A regulation names it the sleep aid; the sleep medicine profession recommends against it
In plain words
Federal regulation recognises exactly two ingredients as over-the-counter sleep aids, and both of them are this drug. The specialist body that reviewed the actual trial evidence drug by drug came to the opposite conclusion and recommended against using it for insomnia.
What was measured
That regulatory recognition as an over-the-counter sleep aid implies demonstrated efficacy for insomnia — the guideline built on the randomised trials recommends the opposite
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
21 CFR 338.10 lists diphenhydramine hydrochloride and diphenhydramine citrate as the only nighttime sleep-aid active ingredients in the over-the-counter monograph. The American Academy of Sleep Medicine convened a four-expert task force, ran a systematic review of randomised controlled trials and applied GRADE to individual drugs rather than classes, and issued the recommendation that clinicians not use diphenhydramine as a treatment for sleep onset or sleep maintenance insomnia in adults, graded WEAK. The gap is not a contradiction between two evidence reviews: the monograph reflects a pre-1962 marketing framework, and the guideline reflects the randomised evidence that has accumulated since.
Written into the record, not signed off as a reviewed claim
Equal itch relief to intravenous cetirizine, and twice as many patients came back
In plain words
In an emergency department trial in people with sudden hives, this drug relieved itching just as well as a modern antihistamine given the same way. But patients on it were more sedated, stayed longer, and were more than twice as likely to return for another visit.
What was measured
Two-hour pruritus score change, treatment centre time, return rate and sedation, against intravenous cetirizine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A multicentre randomised phase 3 noninferiority trial enrolled 262 adults presenting to emergency departments and urgent care centres with acute urticaria requiring an intravenous antihistamine, randomising them to intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The two-hour change from baseline in patient-rated pruritus score was -1.6 for cetirizine against -1.5 for diphenhydramine (95% CI -0.1 to 0.3), meeting noninferiority in cetirizine’s favour. Secondary endpoints all favoured cetirizine: mean time in the treatment centre 1.7 against 2.1 hours (p=0.005), return to the treatment centre 5.5% against 14.1% (p=0.02), and two-hour change in sedation score 0.1 against 0.5 (p=0.03).
Written into the record, not signed off as a reviewed claim
Cumulative anticholinergic exposure tracks with dementia, and this is an observation
In plain words
A long-running study of older adults found that the more anticholinergic medicine someone had taken over ten years, the more likely they were to develop dementia. First-generation antihistamines were one of the three commonest drug groups involved. This is an association measured in a population, not a demonstration that the drug causes the disease.
What was measured
That taking diphenhydramine causes dementia — the cohort measured cumulative exposure across a whole drug class and reports an association with a dose-response gradient, which is suggestive and is not a causal demonstration
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Adult Changes in Thought cohort followed 3,434 participants aged 65 and over with no dementia at entry, using computerised pharmacy dispensing records to compute total standardised daily doses of anticholinergics over ten years, excluding the most recent twelve months to avoid capturing prodromal use. Over a mean 7.3 years, 797 participants (23.2%) developed dementia, 637 of them Alzheimer disease. A ten-year cumulative dose-response relationship was observed (test for trend p<0.001), with adjusted hazard ratios against non-use of 0.92 (95% CI 0.74 to 1.16) for 1 to 90 total standardised daily doses, 1.19 (0.94 to 1.51) for 91 to 365, 1.23 (0.94 to 1.62) for 366 to 1,095 and 1.54 (1.21 to 1.96) above 1,095. The three commonest classes were tricyclic antidepressants, first-generation antihistamines and bladder antimuscarinics. The design cannot separate the drug from the reason it was prescribed, and the authors framed the finding as a reason to minimise exposure rather than as proof of causation.
Written into the record, not signed off as a reviewed claim
It is one of the commonest agents in adolescent self-poisoning
In plain words
Because it is cheap, unrestricted and in every house, it turns up constantly in deliberate overdoses. Poison centre records show tens of thousands of adolescent cases, rising over time, and the largest ingestions cause life-threatening effects in about one in five.
What was measured
National Poison Data System case counts, admission rates and major-effect rates by ingestion size
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A National Poison Data System analysis of 47,644 diphenhydramine ingestions in 13 to 19 year-olds between 2007 and 2020 found rising case numbers, a rising proportion of intentional ingestions and a rising proportion of suspected suicide, with cardiac complications, seizures, coma and death more common after intentional ingestion than after misuse or abuse. A separate NPDS time-series of 24,358 cases in 6 to 18 year-olds from 2016 to 2023 found a 34.3% increase in ingestions, with 1,190 (4.9%) classified as massive; massive ingestions required inpatient admission in 69.6% of cases against 26.2% for non-massive, and produced major effects — life-threatening symptoms, residual disability or death — in 21.3% against 1.0%. FDA issued a warning about intentional misuse and abuse of diphenhydramine in September 2020.
Written into the record, not signed off as a reviewed claim
Eighty years on the market is not eighty years of evidence
In plain words
This drug reached pharmacies in 1946, sixteen years before manufacturers were first required to prove that a medicine works. Most of what is claimed for it has never been tested the way a new drug would be tested today.
What was measured
That long-standing availability and regulatory recognition constitute evidence of effectiveness — they are facts about the history of drug regulation, and the randomised trials that exist point the other way
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Diphenhydramine was introduced in the United States in 1946. The Kefauver-Harris amendment of 1962 first required substantial evidence of effectiveness for approval. Today the drug is not marketed under a modern new drug application at all: over-the-counter sale runs under the FDA monograph system, and the CMS acquisition survey lists 120 separate products. Where randomised trials have been run against the specific claims — infant sleep in TIRED, adult insomnia in the evidence base the American Academy of Sleep Medicine reviewed, tolerance to sedation over four days — the results have been null or negative. The strongest positive randomised result on this page comes from a trial designed to show that a different drug could replace it.
Source
21 CFR 338, Nighttime Sleep-Aid Drug Products for Over-the-Counter Human Use; Merenstein D et al., Arch Pediatr Adolesc Med 2006;160:707-712; Sateia MJ et al., J Clin Sleep Med 2017;13:307-349
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
TC2D6JAD40
CAS registry number
58-73-1
PubChem compound
3100
RxNorm concept
1362
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: Reviewed first-read answer.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
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.
What the approval register records
109 approved applications cover products containing this substance. The earliest was NDA005845, approved 19460304 to MCNEIL CONS.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 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.
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.
The first prescription antihistamine, an H1 antagonist that crosses freely into the brain and also blocks muscarinic receptors — it was non-inferior to intravenous cetirizine on two-hour itch relief in 262 patients with acute urticaria while sending twice as many of them back for a second visit, it impaired simulated driving more than a 0.1% blood alcohol concentration, its sedative effect disappeared completely by day four of continuous use, and it failed outright as an infant sleep aid in a randomised trial that a safety board stopped early.
Recorded evidence blocks (13)
Q1
What did Diphenhydramine's largest trial (140660 people) and its longest (24 years) measure?
140660 people in Diphenhydramine's largest registered study, 24 years in its longest registered window, measuring Change From Baseline Short Form (SF)-12/36 Physical Function Over the Course of the Year After Injury. ClinicalTrials.gov · 2026-09-01
76 phase2, 49 phase1, 40 na, 37 phase3, 25 phase4, 8 na or unstated, 4 early phase1; NCT00961792; 2027-10. Last human test completed 2026, NCT05910762.
Interpretation These counts include studies where Diphenhydramine was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
76
phase1
49
na
40
phase3
37
phase4
25
na or unstated
8
2 more recorded rows
early phase1
4
Last recorded human testNCT05910762
2026-07-31
recorded 2026-09-01 · last checked 2026-09-04
Q2
From rat to human: where has Diphenhydramine shown lifespan?
"The response rate observed in the phase 1 portion of the study did not merit further evaluation in phase 2 portion of the study."; 32 of 220 registered studies
Show the evidence
Trial
NCT00226941
terminated; "The response rate observed in the phase 1 portion of the study did not merit further evaluation in phase 2 portion of the study."
NCT00381810
terminated; "During a safety review of studies U2970g and U2971g, the Data Monitoring Committee recommended that enrollment in this extension trial be terminated."
NCT00429702
terminated; "Closed due to poor accrual and lack of feasibility to finish study per DSMB"
NCT00482053
terminated; "Low accrual"
NCT00505531
terminated; "Not enough data to analyze the results."
NCT00927329
withdrawn; "Original PI left institution."
14 further recorded trials
NCT01067677
withdrawn; "We do not have the funding or resources to complete the study at this time"
NCT01289938
terminated; "To unsuccessful recruitment of rare UM-genotype. All other planned genotype groups are completed (EM, IM and PM)."
NCT01455389
terminated; "Trial terminated by sponsor after decision to evaluate combination of quaratusugene ozeplasmid and osimertinib instead of further evaluating quaratusugene ozeplasmid and erlotinib."
NCT02029638
terminated; "Slow accrual"
NCT02098499
withdrawn; "No recruitment occurred and PI retired"
NCT02179814
suspended; "Conduct of the first analyses"
NCT02188719
terminated; "The trial could not be completed within the grant timeline."
NCT02363946
terminated; "Company decision to terminate the trial"
NCT02452528
terminated; "Company decision to discontinue trial"
NCT02577029
terminated; "Company decision to discontinue trial"
NCT02604199
terminated; "Company decision to discontinue trial"
NCT02604212
terminated; "Company decision to discontinue trial"
NCT02613910
terminated; "Novartis has acquired the rights to ofatumumab and terminated the OPV116910 and OPV117059 studies. This decision is not linked to any safety consideration."
NCT02738008
terminated; "Company decision to discontinue trial"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Diphenhydramine used Diphenhydramine 25 mg — over how long?
5 recorded sentences naming Diphenhydramine; u-shaped, dose-response, dose response, biphasic
Show the evidence
u-shapedPMID 22971351
"Chloroquine scratching displayed an inverse u-shaped dose response curve, which was insensitive to diphenhydramine."
dose-responsePMID 41562034
"Four NADs with different mechanisms of action were included at a high (mg/L) and low (μg/L) dose to establish dose-response relationships: chlorpromazine (antipsychotic), diclofenac (anti-inflammatory), diphenhydramine (antihistamine), and fluoxetine (antidepressant)."
dose responsePMID 27308885
"OBJECTIVE To characterize the signalment, dose response, and clinical signs of diphenhydramine toxicosis in dogs."
dose-responsePMID 22044917
"After rats were injected intrathecally with diphenhydramine and pheniramine, the dose-response curves were obtained."
biphasicPMID 16702624
"Diphenhydramine inhibited the spontaneous, Fe(II)-induced and Fe(II)/ascorbate-induced lipid peroxidation, while famotidine showed a biphasic concentration-dependent effect on spontaneous lipid peroxidation (a stimulation by 1 mM and an inhibition by 5 mM) and increased Fe(II)-induced- and inhibited Fe(II)/ascorbate-induced lipid peroxidation in the rat liver and brain."
recorded 2025-10-07 · last checked 2026-09-04
Q6
Could one person measure Diphenhydramine's effect on response rate?
Response rate: measured in Diphenhydramine's trials.
Interpretation response rate is the recorded endpoint.
dose limiting toxicity number of dlts by treatment group; 2026-09-01
dose limiting toxicity number of affected; 2026-09-01
14 more recorded rows
biomarkers
progression free survival in advanced stage dlbcl; 2026-09-01
biomarkers
at least 1 serious adverse event; 2026-09-01
biomarkers
event free survival per protocol; 2026-09-01
biomarkers
clinical response rate; 2026-09-01
biomarkers
tramadol er reduces vas for oih; 2026-09-01
biomarkers
overall survival at 2 years and 5 years; 2026-09-01
biomarkers
likert scale for satisfaction; 2026-09-01
biomarkers
pain intensity; 2026-09-01
biomarkers
pharmacokinetic parameters; 2026-09-01
biomarkers
urticaria activity 7 from baseline to week 4; 2026-09-01
biomarkers
bmi z; 2026-09-01
biomarkers
incidence of graft versus host disease; 2026-09-01
biomarkers
toxicity; 2026-09-01
biomarkers
resting metabolic rate; 2026-09-01
human trials at or under30
76
Not recorded for this substance
a recorded half-life
smallest human trial
0; NCT00927329; PHASE1; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q7
Which of acute rejections in all enrolled, adverse effects and adverse events did Diphenhydramine's trials measure?
acute rejections in all enrolled, adverse effects and adverse events lead 40 outcome terms across Diphenhydramine's trials. ClinicalTrials.gov · 2026-09-01
chronic graft vs host disease, dose limiting toxicity number of dlts by treatment group, dose limiting toxicity number of affected, progression free survival in advanced stage dlbcl, at least 1 serious adverse event and event free survival per protocol follow.
Show the evidence
response rate
1
relapse free complete clinical response
1
acute rejections in all enrolled
1
chronic graft vs host disease
1
dose limiting toxicity number of dlts by treatment group
1
dose limiting toxicity number of affected
1
14 more recorded rows
progression free survival in advanced stage dlbcl
1
at least 1 serious adverse event
1
event free survival per protocol
1
clinical response rate
1
tramadol er reduces vas for oih
1
overall survival at 2 years and 5 years
1
likert scale for satisfaction
1
pain intensity
1
pharmacokinetic parameters
1
urticaria activity 7 from baseline to week 4
1
bmi z
1
incidence of graft versus host disease
1
toxicity
1
resting metabolic rate
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Diphenhydramine's 42 ongoing trials reports first?
Subjective response to alcohol and other common substances utilizing mood questionnaires in adult drinkers; Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR); latest 2033-11-16
Show the evidence
Trial
NCT00961792
"Chicago Social Drinking Project"; n 800; "Subjective response to alcohol and other common substances utilizing mood questionnaires in adult drinkers"; 2027-10
NCT01059786
"Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia"; n 69; "Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR)"; 2031-06-30
NCT03582891
"The Motor Network in Parkinson's Disease and Dystonia: Mechanisms of Therapy"; n 25; "Duration of 'on' stimulation time without dyskinesia from motor diaries in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)"; 2028-03
NCT03805932
"Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia"; n 18; "Recommended Safe Dose of Moxetumomab Pasudotox-tdfk"; 2029-06-30
NCT03840083
"Sleep-dependent Learning in Aging"; n 584; "Change in memory accuracy for intervention compared to control"; 2025-07-15
NCT04221477
"A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With ISN/RPS 2003 Class III or IV Lupus Nephritis"; n 271; "Percentage of Participants With Complete Renal Response (CRR)"; 2031-03-02
14 further recorded trials
NCT04224558
"Stem Cell Transplantation in Crohn's Disease"; n 15; "Change in mucosal healing"; 2027-09-30
NCT04268498
"A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma"; n 310; "Rate of Minimal Residual Disease (MRD) Negativity"; 2027-02-01
NCT04367883
"Influenza Vaccination, ACEI and ARB in the Evolution of SARS-CoV2 Infection"; n 3000; "hospital output"; 2028-02-24
NCT04544436
"A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)"; n 864; "Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)"; 2028-08-31
NCT04548999
"A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)"; n 769; "Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)"; 2027-09-08
NCT04629248
"A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy"; n 142; "Percentage of Participants who Achieve a Complete Remission (CR) at Week 104"; 2027-12-21
NCT04743661
"131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma"; n 62; "2-year event free survival (EFS) in the Recurrent Medulloblastoma Cohort"; 2027-09-30
NCT04862221
"TReatment for ImmUne Mediated PathopHysiology"; n 44; "Survival with native liver (SNL)"; 2027-02
NCT04963296
"A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus"; n 303; "Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52"; 2028-03-13
NCT05039619
"A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants"; n 40; "Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)"; 2030-06-14
NCT05206227
"Histamine as a Molecular Transducer of Adaptation to Exercise"; n 80; "Percentage of mast cell degranulation"; 2027-03-31
NCT05211336
"Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System"; n 14; "Proportion of Participants Who Completed at Least 2 Cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) Therapy Without Stopping Due to Toxicity"; 2029-06-01
NCT05319730
"A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)"; n 230; "Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) During Safety Lead-in Phase"; 2029-04-10
NCT05405166
"SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM"; n 531; "Overall Response Rate (ORR)"; 2027-03-23
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which running trial of Diphenhydramine could settle lifespan?
NCT04862221 measures Survival with native liver (SNL), reading out 2027-02.
2 open trials; n 44; "TReatment for ImmUne Mediated PathopHysiology"
Show the evidence
Trial
NCT04862221
"TReatment for ImmUne Mediated PathopHysiology"; n 44; "Survival with native liver (SNL)"; 2027-02
NCT04743661
"131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma"; n 62; "2-year event free survival (EFS) in the Recurrent Medulloblastoma Cohort"; 2027-09-30
Q10
Which 48 trials of Diphenhydramine posted no result?
Posted no result
48 of 48 completed trials
Registrations
NCT00000363, NCT00137202, NCT00662337, NCT00648973, NCT00801749 and NCT00762749, and 42 more
Completion dates
oldest 2001-06; newest 2024-05-25
Show the evidence
Trial
NCT00000363
2001-06
NCT00137202
2006-05
NCT00662337
2006-11
NCT00648973
2007-05
NCT00801749
2008-03
NCT00762749
2008-11
14 further recorded trials
NCT01071811
2009-01
NCT01858090
2010-01
NCT01648062
2010-04
NCT00935402
2010-07
NCT01411124
2011-10
NCT01666678
2012-03
NCT01837446
2012-10
NCT01712828
2013-01-01
NCT01985789
2014-05
NCT02463929
2014-07
NCT01493661
2015-02
NCT02128737
2015-04
NCT02130791
2015-11
NCT01669967
2015-12
Q11
At the median, Diphenhydramine's trials enrolled 45 people — anything larger?
Median enrolment
45
Largest enrolment
140660
Registered trials counted
217
Q12
What do 1807 spontaneous reports say about Diphenhydramine — 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.
Diphenhydramine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1807 reaction mentions were counted: drug hypersensitivity 414; nausea 245; headache 220; vomiting 154. open-targets-adr · CHEMBL1201089 · 2026-06-24
Show the evidence
drug hypersensitivity
414
nausea
245
headache
220
vomiting
154
dizziness
151
decreased appetite
146
4 more recorded rows
weight decreased
124
pharyngitis
120
ear infection
119
abdominal discomfort
114
recorded 2026-06-24 · last checked 2026-09-04
Q13
What is recorded about Diphenhydramine and autophagy?
"In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy." — where Diphenhydramine and autophagy appear together. Europe PMC · pathway abstract search · 2024-04-01
autophagy; PMID 38556548
Show the evidence
autophagyPMID 38556548
"In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy."
recorded 2024-04-01 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md
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✓ source coverage passed: 9 source rows
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