The antihistamine in Benadryl can wind some people up instead of down
Diphenhydramine, best known as Benadryl, is famous for making people drowsy, which is why it turns up in so many sleep aids. Yet in some users, especially at higher doses, it does the opposite, causing agitation and restlessness. Sleep specialists have also questioned how well it actually works for insomnia.
George Rieveschl developed the drug, and it entered commercial use in 1946. It is a first-generation H1 antihistamine, meaning it blocks histamine, and also a strong anticholinergic. It can be swallowed, injected into a vein or muscle, or applied to the skin, with oral doses peaking at about two hours and lasting up to seven. It is now generic, and in 2023 American doctors wrote over 700,000 prescriptions for it, placing it 294th on the national list.
Its main uses are allergies, itching, insomnia and cold symptoms, and as of 2007 it was the antihistamine most used for acute allergic reactions in emergency departments. By injection it is often given alongside epinephrine in anaphylaxis, though that role had not been properly studied as of 2007. Creams, gels, sprays and eye drops relieve itching with less drowsiness than tablets. It also has anti-nausea properties and is the active ingredient in Dramamine, known as Gravol, while doses above the recommended amount, especially over 200 mg, can themselves cause nausea. Less commonly it is used for parkinsonism and for acute dystonia triggered by older antipsychotics, and it has served as a local anaesthetic for people allergic to lidocaine.
The sleep question is contested. The American Academy of Sleep Medicine's 2017 guidelines advised against it for insomnia, citing weak effectiveness and poor evidence, and a large 2022 network meta-analysis found little evidence either way. It can also produce mild psychological dependence. Sleepiness, clumsiness and stomach upset are common side effects; no clear harm has been shown in pregnancy, but it is not recommended while breastfeeding.
Some parents have given it to children to make them sleep on long flights, drawing criticism from doctors and airline staff: a sedated passenger may react poorly in an emergency, and a paradoxical reaction can leave a child hyperactive. In a 2009 article, Seattle Children's Hospital argued that parental convenience never justifies medicating a child. Its sedating and deliriant effects have also led to occasional recreational misuse.
Source: Diphenhydramine
