Diphenhydramine

Diphenhydramine, 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 and it works by blocking certain effects of histamine, which produces its antihistamine and 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 a dose, and effects can last for up to seven hours.

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.

It was developed by George Rieveschl and put into commercial use in 1946. It is available as a generic medication. In 2022, it was the 258th most commonly prescribed medication in the United States, with more than 1 million prescriptions.

Its sedative and deliriant effects have led to some cases of recreational use.