Diphenhydramine (DPH) is an antihistamine and sedative used primarily to treat allergies, insomnia, and common cold symptoms. It's also less commonly used to treat tremors and nausea in Parkinson's disease. It can be taken orally, injected into a vein, injected into a muscle, or applied to the skin. Maximum effects are usually around two hours after taking the drug, and effects can last up to seven hours.

Common side effects include drowsiness, poor coordination, and stomach upset. Not recommended for use by young children or the elderly. There is no apparent risk of harm when used during pregnancy; however, use during breastfeeding is not recommended. It is a first-generation H1-antihistamine that works by blocking some of the effects of histamine, thereby producing antihistamine and sedative effects. Diphenhydramine is also a potent anticholinergic, which means it can act as a delirium at much higher doses than recommended. Its sedative and comatose effects have led to some cases of recreational use.

Diphenhydramine was originally developed by George Rieveschl and became commercially available in 1946. It is available as a generic drug. It is sold under brand names such as Benadryl. In 2020, it was the 192nd most commonly prescribed drug in the United States, with more than 2 million prescriptions filled.

medical use

diphenhydramine tablets

Diphenhydramine is a first-generation antihistamine used to treat a variety of conditions, including allergic symptoms and itching, the common cold, insomnia, motion sickness, and extrapyramidal symptoms. Diphenhydramine also has local anesthetic properties and has been used in people allergic to common local anesthetics such as lidocaine.


Diphenhydramine is effective in treating allergies. As of 2007, it is the most commonly used antihistamine for emergency treatment of acute allergic reactions.

In addition to epinephrine, it is often used by injection to treat allergic reactions, although as of 2007 its use for this purpose has not been properly studied. Its use is recommended only after acute symptoms have improved.

A bottle of topical “anti-itch gel” diphenhydramine

Diphenhydramine is available in topical preparations, including creams, lotions, gels, and sprays. These are used to relieve itching and have the advantage of causing fewer systemic effects (such as drowsiness) than oral forms.

Movement disorders

Diphenhydramine is used to treat antipsychotic-induced akathisia and Parkinson's disease-like extrapyramidal symptoms. It is also used to treat acute dystonia, including torticollis and ocular crises, caused by first-generation antipsychotics.


Due to its sedative effects, diphenhydramine is widely used as an over-the-counter sleep aid to treat insomnia. This medication is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients, such as acetaminophen (acetaminophen) in Tylenol PM and ibuprofen in Advil PM. Diphenhydramine can cause mild psychological dependence. Diphenhydramine is also used as an anti-anxiety medication.

Parents have also used diphenhydramine over-the-counter to try to put their children to sleep and to calm them during long flights. This has been criticized by doctors and members of the aviation industry because sedating passengers could put them at risk if they are unable to respond effectively to an emergency, as well as the drug's side effects, not least the potential for inconsistencies Reactions may make some users hyperactive. In response to this use case, Seattle Children's Hospital stated in a 2009 article that "the use of medications for convenience is never an indication for use in children."

The American Academy of Sleep Medicine's 2017 Clinical Practice Guidelines recommend against using diphenhydramine to treat insomnia due to poor efficacy and low-quality evidence. A major systematic review and network meta-analysis of medications for insomnia published in 2022 found little evidence for the use of diphenhydramine to treat insomnia.


Diphenhydramine also has antiemetic properties and can be used to treat nausea caused by vertigo and motion sickness. However, nausea may occur when taking more than the recommended dose (especially over 200 mg).

Special groups

Diphenhydramine is not recommended for people over 60 and children under 6 years old unless they consult a doctor. These individuals should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine. Because diphenhydramine has strong anticholinergic effects, it is on Beers' list of drugs that seniors should avoid.

Diphenhydramine is excreted in breast milk. Occasional administration of low doses of diphenhydramine is not expected to cause adverse effects in breastfed infants. High doses and long-term use may affect the infant or reduce breast milk supply, especially when used concomitantly with sympathomimetics (such as pseudoephedrine) or before lactation is established. Taking a single dose at bedtime after the last feeding of the day can minimize the harmful effects of the medication on the baby and milk supply. Nonetheless, non-sedating antihistamines are preferred.

Paradoxical reactions have been documented with diphenhydramine, particularly in children, and it may cause euphoria rather than sedation.

Topical diphenhydramine is sometimes used specifically for hospice patients. There are no indications for this use, and topical diphenhydramine should not be used as a treatment for nausea because research has not shown that this treatment is more effective than other treatments.

There are no documented cases of clinically apparent acute liver injury caused by normal doses of diphenhydramine.

Negative Effects

The most prominent side effect is sedation. A typical dose causes impaired driving equivalent to a blood alcohol concentration of 0.10, which is higher than the 0.08 limit under most drunk driving laws.

Diphenhydramine is a potent anticholinergic drug that may cause delirium at high doses. This activity can cause side effects such as dry mouth and throat, increased heart rate, dilated pupils, urinary retention, constipation, and at high doses, hallucinations or delirium. Other side effects include movement disorders (ataxia), skin flushing, blurred near vision due to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia), sedation, difficulty concentrating, and short-term memory loss. , visual disturbances, irregular breathing, dizziness, irritability, itchy skin, confusion, increased body temperature (usually of the hands and/or feet), temporary erectile dysfunction, and euphoria. Although it can be used to treat nausea, it is more High doses may cause vomiting. Overdose of diphenhydramine may sometimes cause QT prolongation.

Some people can have an allergic reaction to diphenhydramine in the form of hives.

Elevated diphenhydramine concentrations may worsen conditions such as restlessness or akathisia, especially at recreational doses. Like other first-generation antihistamines, normal doses of diphenhydramine can worsen the symptoms of restless legs syndrome. [49] Because diphenhydramine is extensively metabolized by the liver, individuals with hepatic impairment should use this drug with caution.

The use of anticholinergic drugs in later life is associated with an increased risk of cognitive decline and dementia in older adults.


Diphenhydramine is contraindicated in premature infants and newborns, as well as in those who are breastfeeding. It is a pregnancy category B drug. Diphenhydramine has additive effects with alcohol and other CNS depressants. Monoamine oxidase inhibitors prolong and potentiate the anticholinergic effects of antihistamines.


Diphenhydramine is one of the most commonly abused over-the-counter drugs in the United States. In the case of overdose, acute diphenhydramine poisoning can have serious or even fatal consequences if left untreated. Overdose symptoms may include:

  • stomach ache
  • Speech abnormalities (difficulty hearing, forced speech, etc.)
  • acute megacolon
  • Anxiety/Nervousness
  • coma
  • die
  • delirium
  • get lost
  • dissociate
  • Feelings of euphoria or irritability
  • Extreme sleepiness
  • flushing of skin
  • Hallucinations (auditory, visual, tactile, etc.)
  • Palpitations
  • unable to urinate
  • Movement disorders
  • muscle spasms
  • epileptic seizure
  • severe dizziness
  • Severe dryness of mouth and throat
  • tremor
  • Vomit

Acute poisoning can be fatal, leading to cardiovascular collapse and death within 2-18 hours, and is generally treated with a symptomatic and supportive approach. Toxicity diagnosis is based on history and clinical manifestations, and in general, precise plasma levels do not appear to provide useful relevant clinical information. Multiple levels of evidence strongly suggest that diphenhydramine (similar to chlorpheniramine) blocks delayed rectifier potassium channels, thereby prolonging the QT interval and leading to arrhythmias such as torsade de pointes. There is currently no specific antidote for diphenhydramine toxicity, but anticholinergic syndrome has been treated with physostigmine in severe delirium or tachycardia. For people who are prone to these symptoms, benzodiazepines can be used to reduce the likelihood of psychosis, agitation, and seizures.


Alcohol may increase drowsiness caused by diphenhydramine.


Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati. In 1946, it became the first prescription antihistamine approved by the U.S. FDA.

In the 1960s, diphenhydramine was found to weakly inhibit the reuptake of the neurotransmitter serotonin. This discovery led to the search for a viable antidepressant with a similar structure and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI). Previously, similar research had synthesized the first SSRI, zimeridine, from brompheniramine (also an antihistamine).

society and culture

Due to its potentially serious side effects and limited euphoric effects, diphenhydramine is considered to have limited abuse potential in the United States, and diphenhydramine is not a controlled substance. Since 2002, the US FDA has required special label warnings for many products containing diphenhydramine. In some jurisdictions, diphenhydramine is frequently present in autopsy specimens collected during sudden infant death investigations; the drug may play a role in these incidents.

Diphenhydramine is one of the banned and controlled drugs in the Republic of Zambia and travelers are advised not to bring this drug into the country. Several Americans have been detained by the Zambia Anti-Narcotics Commission for possession of Benadryl and other over-the-counter medicines containing diphenhydramine.

abuse and addiction

Although diphenhydramine is widely used and generally considered safe for occasional use, multiple cases of abuse and addiction have been documented. Because the drug is cheap and available over the counter in most countries, teenagers who don't have access to more popular illicit drugs are especially at risk. People with mental health problems, especially those with schizophrenia, are also prone to abusing the drug, which is self-administered in large doses to treat extrapyramidal symptoms caused by antipsychotic use.

Users report sedation, mild euphoria, and hallucinations as expected effects of this drug. Research suggests that antimuscarinic drugs, including diphenhydramine, "may have antidepressant and mood-elevating properties." A study of adult men with a history of sedative abuse found that subjects who took high doses (400 mg) of diphenhydramine reported a desire to take the drug again, although negative effects such as difficulty concentrating, Confusion, tremors, and blurred vision.

In 2020, an online challenge involving intentional overdose of diphenhydramine appeared on the social media platform TikTok; the challenge, known as the "Diphenhydramine Challenge," encouraged participants to take dangerous doses of diphenhydramine The resulting mental repercussions from the filming have been shown to have resulted in multiple hospitalizations and at least two deaths.


Diphenhydramine is marketed by McNeil Consumer Healthcare under the tradename Benadryl in the United States, Canada, and South Africa. Trade names in other countries include Dimedrol, Daedalon and Nytol. It is also available as a generic drug.

Procter & Gamble sells an over-the-counter formulation of diphenhydramine as a sleep aid under the brand name ZzzQuil.


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