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Legal Status
Drug Information
FDA Classification Drug
Class Antihistamine
Sedative Hypnotic
Deliriant Hallucinogen
Addiction Risk Low
Brand names Benadryl, Unisom, Sominex, ZzzQuil

Diphenhydramine, better known by its brand name Benadryl, is a first-generation antihistamine first discovered in the 1940's.

Legality and Availability

Diphenhydramine is legal and unrestricted almost everywhere in the Western world.

In the United States, 600 tablets of 25 mg generic diphenhydramine can be purchased at Costco for about $10.

Zambia is one of the only countries in the world which considers diphenhydramine a controlled substance.

Official Uses


Diphenhydramine limits the effects of histamine in the body, and is effective at reducing symptoms of seasonal allergies, hay fever, and acute allergic responses. It should be noted however that newer antihistamines are equally effective at this in most cases, without the sedative effects.

Motion Sickness

Diphenhydramine is effective at easing symptoms of motion sickness.


Diphenhydramine is sometimes given to patients undergoing antipsychotic treatment to reduce extrapyramidal symptoms.


As this drug is a powerful sedative at 50 mg to 100 mg, it is often used as a sleep aid. Studies show that the body builds tolerance to this effect rapidly, and diphenhydramine is no better than placebo for insomnia after three days. This is why it is considered non-addictive and allowed to be sold over-the-counter as a sleep product.

Unofficial Uses

As a Depressant

At doses at or exceeding the recommendation for insomnia (50 mg to 100 mg), diphenhydramine can produce a "drunken" state. However, most do not find the effects euphoric.

As a Hallucinogen

At doses exceeding 100 mg (the maximum dose indicated in most countries), there can be hallucinogenic properties from diphenhydramine.[1] However, being a deliriant (rather than a psychedelic or dissociative drug), the effects are typically viewed as unpleasant, and abusing the drug habitually is rare.

As an Opioid Potentiator

Diphenhydramine is sometimes used in combination with opioids in order to achieve a greater effect from them.

As an Antidepressant

Diphenhydramine has been investigated for its use as an antidepressant. The drug has been found to have SSRI-like properties, and can cause a modest increase in serotonin levels.

One study comparing OCD treatments used diphenhydramine as a placebo, but found that it caused a significant reduction in symptoms.[2][3]


Diphenhydramine is metabolized primarily by the CYP2D6 enzyme. Similar to dextromethorphan and other drugs metabolized by this enzyme, individuals who are unusually slow or rapid metabolizers may experience different effects. Among those with a CYP2D6 deficiency, mild hallucinogenic effects have been reported from a typical dose for hay fever (25 to 50 mg) or sedation (50 mg or more).


  1. https://www.erowid.org/pharms/diphenhydramine/diphenhydramine_dose.shtml
  2. https://www.ncbi.nlm.nih.gov/pubmed/1474179
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181958/