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Deliriant · Depressant

Diphenhydramine

Also called DPH, Benadryl, Nytol, Sominex, Unisom SleepMelts, ZzzQuil

Original Wikipedia articleen.wikipedia.org/wiki/Diphenhydramine revision used (24 October 2026)

Why a "revision used" link? Anyone can edit Wikipedia at any time, so the article you open today may not say what it said when we read it. This link opens the exact version we read on 24 October 2026, frozen as it was. It is the only way to check that every quote on this page matches its source word for word. Newer versions may correct or change things. When we re-check this page against a newer version, the edit log records it. How we cite

Common dose · Oral200–400 mg PW
Onset30–90 minutes PW
Total3–10 hours PW
After-effectsup to 24 hours PW

Dosage

When sources disagree, both rows are shown as published. Nothing is averaged or merged.

Oral

SourceThresholdLightCommonStrongHeavy
PsychonautWiki25 mg PW100–200 mg PW200–400 mg PW400–700 mg PW700 mg+ PW
TripSit–100–250 mg TS200–500 mg TS450–700 mg TS–

Bioavailability: 40–60% PW

NOTE: The doses provided are for recreational usage. For use as a sleep aid the dose ranges from 25-100mg, or as specified on the product packaging. TS

TripSit dose text

TripSit's factsheet also states its doses as text.

Oral Light: 100-250mg Common: 200-500mg Strong: 450-700mg NOTE: The doses provided are for recreational usage. For use as a sleep aid the dose ranges from 25-75mg, or as specified on the product packaging. For medical allergy use doses tend to range from 25-50mg, or as specified on the product packaging. TS

What dose are you on? (self-reported, unverified)
Read this first. These numbers come from anonymous visitors typing in a box. Nobody checks them. People misjudge, mistype, troll, or take untested products of unknown strength. They are not a dose guide and never override the sourced table above. They exist only so the sourced ranges can be compared with what people say they take. If you are deciding what to take, use the sourced table, start low, and read the risks section.
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Duration

Route · sourceOnsetCome-upPeakOffsetTotalAfter-effects
Oral · PsychonautWiki30–90 minutes PW45–90 minutes PW1–4 hours PW2–6 hours PW3–10 hours PWup to 24 hours PW

TripSit factsheet

Onset
60-120 minutes TS
Duration
6-8 hours TS
Aftereffects
1-12 hours TS

Mixing

Acute combinations: what happens when these are taken close together. Entries backed by a medical journal or agency are listed first.

Backed by medical journals

  • Selective serotonin re-uptake inhibitors (SSRIs) - SSRIs can suppress the visual effects of diphenhydramine. However, this combination may elevate the risk of serotonin syndrome due to diphenhydramine's weak serotonergic effects.[13] PW⚠ PsychonautWiki lists this combination without a danger rating.

Other documented combinations

  • Stimulants - Due to diphenhydramine's excitatory cardiac effect, combining it with stimulants poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack, as well as other cardiovascular events. PW⚠ PsychonautWiki lists this combination without a danger rating.
  • Benzodiazepines - Benzodiazepines can suppress the visual effects of diphenhydramine. However, this combination can produce a dangerous amount of sedation and respiratory depression. PW⚠ PsychonautWiki itself has flagged this text: citation needed.⚠ PsychonautWiki lists this combination without a danger rating.
  • Anticholinergics - Due to diphenhydramine's excitatory cardiac effect, combining it with other anticholinergics poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack, as well as other cardiovascular events (inhibition of acetylcholine causes increased heart rate). PW⚠ PsychonautWiki lists this combination without a danger rating.

TripSit combination chart

TripSit rates each pairing. Only pairings with a number carry a citation from TripSit. See the whole chart, with TripSit's note for every pairing.

Dangerous

ghb/gbl[14–17] TS

Risks and toxicity

The toxicity and long-term health effects of recreational diphenhydramine use have not been studied extensively. PW

Diphenhydramine can be highly unpredictable, and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization, or death. Additionally, diphenhydramine puts users in a state where they have little control over their actions. Diphenhydramine can provoke bizarre and nonsensical behavior, which may put the user at risk. PW

Anecdotal reports suggest that regular use of diphenhydramine can have profound effects on one's kidneys and bladder, with the potential to result in issues similar to that of ketamine cystitis. PW

Cumulative diphenhydramine use has been tentatively linked to an increased risk of developing dementia.[18] PW

Some chronic users also report the worsening of mental illnesses (e.g. depression, anxiety disorders, schizophrenia) PW⚠ PsychonautWiki itself has flagged this text: citation needed.

Overdose

The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals or individuals taking other drugs alongside it can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include delirium, psychosis, anxiety, confusion, hypotension, dryness, urinary retention, dizziness, dilated pupils and increased heart rate. Some of the more serious side effects at these doses include an even higher risk of seizures and dangerous cardiovascular effects such as arrhythmia (abnormal heartbeat).[19] PW

The user may be completely unable to distinguish reality from hallucinations. For this reason, there is a significant risk of the user responding to a delusional environment and injuring themselves or others, as well as the possibility of engaging in too much physical activity which can further strain the heart or cause rhabdomyolysis. Individuals experiencing delusions should, if possible, not be agitated. The first line of treatment for overdose should be benzodiazepines, although medical attention should always be sought.[20] PW

Diphenhydramine can become fatal at amounts close to or exceeding 2 grams. This can result in death, especially when combined with most stimulants, depressants, and MAOIs. PW⚠ PsychonautWiki itself has flagged this text: citation needed.

Psychosis

Some anecdotal reports suggest that diphenhydramine causes psychosis and delirium at a significantly higher rate than other hallucinogens (i.e. psychedelics and dissociative). There are a large number of experience reports online that describe states of psychotic delirium, amnesia, and other serious consequences after abusing the substance. In many cases, it has resulted in hospitalization and death. PW⚠ PsychonautWiki itself has flagged this text: citation needed.

The recreational use of diphenhydramine is generally not advised. If deciding to use this substance, one should use extreme caution and harm reduction practices, such as having a sober trip sitter. PW

Dependence and abuse potential

Diphenhydramine produces dependence with chronic use. In comparison to other hallucinogens, DPH has been reported to have significantly less abuse potential than other hallucinogens. Most people who try it do not wish to repeat the experience. PW

Tolerance to many of the effects of DPH develops with repeated use. Users have to administer increasingly large doses to achieve the impact. After that, it takes about 1 - 2 weeks for tolerance to return to baseline (in the absence of further consumption). DPH presents cross-tolerance with all deliriants, meaning that after the consumption of DPH, all deliriants will have a reduced effect. PW

TripSit factsheet

Avoid
Many oral diphenhydramine preparations contain analgesics such as acetaminophen/paracetamol or aspirin, which can be toxic to the liver in high doses.[1] TS

Testing

Awaiting sourceReagent reactions and test kit guidance from a harm reduction testing service.

Effects

Delirium, dream-like experiences, paranoia, visual and audio distortions, dry mouth, muscle cramps, nausea, dysphoria, tremors. Often described as a pretty negative experience. TS

Overview

Diphenhydramine (also known as DPH, Dimedrol, Benadryl, and many others) is a deliriant substance of the ethanolamine class. It is a first-generation H₁ antihistamine that is widely used as a generic, over-the-counter medication to treat allergies. When exceeding approved doses, diphenhydramine produces powerful deliriant effects. PW

An antihistamine which, when taken in smaller doses relieves allergies and insomnia. In larger doses works as a deliriant and can actually keep the user awake. Generally the 'high' of this drug is reported as dysphoric, potentially causing hallucinations indistinguishable from reality.[1] TS

Diphenhydramine, or Diphenylhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particularly at higher doses. This may manifest as agitation, anxiety, or restlessness rather than sedation. It is a first-generation H₁-antihistamine (i.e. it blocks histamine) with sedative effects. Diphenhydramine is also a potent anticholinergic. It is mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after an oral dose, and effects can last for up to seven hours.[2–6] WP

Common side effects include sleepiness, poor coordination, and an upset stomach. There is no clear risk of harm when used during pregnancy; however, use during breastfeeding is not recommended.[4][7] WP

It was developed by George Rieveschl and put into commercial use in 1946. It is available as a generic medication. In 2023, it was the 294th most commonly prescribed medication in the United States, with more than 700,000 prescriptions.[4][8–11] WP

Its sedative and deliriant effects have led to some cases of recreational use.[5][12] WP

History

History

In 1943, diphenhydramine was discovered by chemist George Rieveschl and one of his students, Fred Huber, while they were conducting research into muscle relaxants at the University of Cincinnati. Huber first synthesized diphenhydramine. Rieveschl then worked with Parke-Davis to test the compound, and the company licensed the patent from him. In 1946, it became the first prescription antihistamine in the United States approved by the FDA.[21][22][23] WP

In the 1960s, diphenhydramine was found to weakly inhibit reuptake of the neurotransmitter serotonin. This discovery led to a search for viable antidepressants with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI). A similar search had previously led to the synthesis of the first SSRI, zimelidine, from brompheniramine, also an antihistamine.[24][25][26] WP

In 1975, diphenhydramine was still available only by prescription in the US and required medical supervision.[27] WP

Pharmacology

Pharmacodynamics

Diphenhydramine, while traditionally known as an antagonist, acts primarily as an inverse agonist of the histamine H₁ receptor. It is a member of the ethanolamine class of antihistaminergic agents. By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. It also crosses the blood–brain barrier and inversely agonizes the H₁ receptors centrally. Its effects on central H₁ receptors cause drowsiness.[50][51] WP

Diphenhydramine is a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome. The utility of diphenhydramine as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.[52] WP

Diphenhydramine also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic. Diphenhydramine has also been shown to inhibit the reuptake of serotonin. It has been shown to be a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats. The drug has also been found to act as an inhibitor of histamine N-methyltransferase (HNMT).[24][48][53][54][55] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Pharmacokinetics

Oral bioavailability of diphenhydramine is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration. Diphenhydramine, available in various salt forms, such as citrate, hydrochloride, and salicylate, exhibits distinct molecular weights and pharmacokinetic properties. Specifically, diphenhydramine hydrochloride and diphenhydramine citrate possess molecular weights of 291.8 g/mol and 447.5 g/mol, respectively. These variations in molecular weight influence the dissolution rates and absorption characteristics of each salt form.[56–64] WP

The primary route of metabolism is two successive demethylations of the tertiary amine. The resulting primary amine is further oxidized to the carboxylic acid. Diphenhydramine is metabolized by the cytochrome P450 enzymes CYP2D6, CYP1A2, CYP2C9, and CYP2C19.[56][65] WP

The elimination half-life of diphenhydramine has not been fully elucidated, but appears to range between 2.4 and 9.3 hours in healthy adults. A 1985 review of antihistamine pharmacokinetics found that the elimination half-life of diphenhydramine ranged between 3.4 and 9.3 hours across five studies, with a median elimination half-life of 4.3 hours. A subsequent 1990 study found that the elimination half-life of diphenhydramine was 5.4 hours in children, 9.2 hours in young adults, and 13.5 hours in the elderly. A 1998 study found a half-life of 4.1 ± 0.3 hours in young men, 7.4 ± 3.0 hours in elderly men, 4.4 ± 0.3 hours in young women, and 4.9 ± 0.6 hours in elderly women. In a 2018 study in children and adolescents, the half-life of diphenhydramine was 8 to 9 hours. In a 2009 study and review, diphenhydramine had a half-life of 4.3 to 9.3 hours across 7 studies.[56][66–70] WP

Detection in body fluids

Diphenhydramine can be quantified in blood, plasma, or serum. Gas chromatography with mass spectrometry (GC-MS) can be used with electron ionization on full scan mode as a screening test. GC-MS or GC-NDP can be used for quantification. Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for people having ingested diphenhydramine. Quantification can be used to monitor therapy, confirm a diagnosis of poisoning in people who are hospitalized, provide evidence in an impaired driving arrest, or assist in a death investigation.[71][72] WP

Receptor binding · Wikipedia

Diphenhydramine

SiteKᵢ (nM)Species
SERT (Serotonin transporter)3800+Human[39][40][41] WP
NET (Norepinephrine transporter)960–2400Human[39][40][41] WP
DAT (Dopamine transporter)1100–2200Human[39][40][41] WP
5-HT2C780Human[40][41] WP
α1B1300Human[40][41] WP
α2A2900Human[40][41] WP
α2B1600Human[40][41] WP
α2C2100Human[40][41] WP
D₂20000Rat[41][42] WP
H₁9.6–16Human[40][41][43] WP
H₂100000+Canine[41][44] WP
H₃10000+Human[40][41][45][46] WP
H₄10000+Human[41][46] WP
M₁80–100Human[40][41][47] WP
M₂120–490Human[40][41][47] WP
M₃84–229Human[40][41][47] WP
M₄53–112Human[40][41][47] WP
M₅30–260Human[40][41][47] WP
VGSC (Voltage-dependent sodium channel)48000–86000Rat[41][48] WP
hERG (Human Ether-à-go-go-Related Gene)27100 (IC₅₀ (Half-maximal inhibitory concentration))Human[41][49] WP

Chemistry

Formula
C17H21NO PC
CAS number
58-73-1 PC
Molar mass (g/mol)
255.35 PC
IUPAC name (computed by PubChem)
2-benzhydryloxy-N,N-dimethylethanamine PC
SMILES
CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2 PC
InChIKey
ZZVUWRFHKOJYTH-UHFFFAOYSA-N PC
PubChem CID
3100

User reports

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Listings

Erowid Experience Vault listing TS

Link as published on TripSit's factsheet.

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Awaiting sourceTrip report threads and this substance's discussion forum.
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Reddit reddit.com

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Pop culture

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References

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