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Why can alcohol increase the sedative effects of some antihistamines?

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antihistamines, including Benadryl — antihistamine Antihistamines such as Benadryl (diphenhydramine) and Claritin (loratadine) can be purchased without prescriptions. Both of those agents act by blocking H₁ receptors. However, whereas Benadryl binds to those receptors in the central nervous system (CNS), causing drowsiness, Claritin does not readily enter the CNS and thus does not normally cause drowsiness.

Alcohol can increase the sedative effects of certain antihistamines because both substances act as depressants on the central nervous system.1

Many antihistamines, particularly older H1 receptor antagonists like diphenhydramine and promethazine, possess inherent sedative properties. When these drugs are combined with alcohol—which also exerts a depressant effect on the nervous system—their combined action can lead to an intensified sedative response. This interaction can significantly impair a person's performance, including their ability to drive safely.1

It is important to note that while newer antihistamines are designed to avoid crossing the blood-brain barrier and are therefore less likely to cause drowsiness, the older formulations remain potent central nervous system depressants that should not be combined with alcohol.1