Why Does Benadryl Help You Sleep?

Sam asked

I just have a general question regarding Benadryl. I know it is an antihistamine but I am wondering why it makes you tired while other ones don't?

Answer

Benadryl (diphenhydramine) is a "first-generation" antihistamine that is well known to cause sedation and drowsiness. For this reason, it is a common ingredient in over the counter sleep aids such as Tylenol PM and ZzzQuil.

First-generation antihistamines, like Benadryl, are more likely to make you tired when compared to later generation antihistamines, like Claritin (loratadine), because they cross the blood brain barrier and enter the central nervous system (CNS). Doing so, they act as a mild CNS depressant, which causes the sedation you experience.

The Role Of Histamine

While histamine is most commonly associated with allergies and the symptoms we experience (sneezing and watery eyes for example), it is an important neurotransmitter in our body with a wide range of effects. In fact, there are 4 types of histamine receptors (H₁, H₂, H₃ and H₄) in our bodies, all with differing effects. When it comes to Benadryl and other medications we classify as "antihistamines", we are referring to H₁ receptor blockers. H₁ receptors are located all over the body and in the brain.

When we are exposed to an allergen, such as pollen, histamine is released and binds to the H₁ receptor, which in turn produces a variety of effects including:

• Itching
• Swelling (i.e. edema)
• Vasodilation (causing flushing)
• Mucus secretions

Benadryl binds to and blocks H₁ receptors, which reduces the above effects, which is why it is an effective medication for allergic symptoms.

As stated above, histamine and its receptors are also located in the brain. Multiple studies have shown that histamine acts as a mediator of "wakefulness"  and is necessary for:

• Wakefulness
• Alertness
• Reaction time

If histamine is blocked from binding to its receptors in the brain, it can result in sedation and drowsiness, which is just what Benadryl does.

Benadryl Induced Drowsiness

Second-generation antihistamines, like Claritin and Allegra don't cross into the brain. However, Benadryl does, which then binds to histamine receptors. This binding blocks histamine from the receptors and therefore, it will not produce its wakefulness promoting effects, causing sedation.

Benadryl is classified as an "ethanolamine" antihistamine, a sub-class of the first generation antihistamines. Ethanolamine antihistamines readily cross the blood brain barrier and are among the most sedating. Other ethanolamine antihistamines include:  

• Tavist (clemastine)
• Dramamine (Dimenhydrinate)

In addition to Benadryl crossing the blood brain barrier and blocking histamine receptors in the brain, it also has significant anticholinergic effects. An anticholinergic is simply a drug that inhibits the response to acetylcholine, another important neurotransmitter in our bodies. anticholinergic effects include:

• Dry mouth
• Dry eyes
• Confusion
• Sedation
• Increased heart rate

Ethanolamine antihistamines, like Benadryl, generally have greater anticholinergic activity than do other antihistamines, which is another reason that Benadryl causes sedation.

Taking Benadryl For Sleep

While Benadryl isn't recommended by the American Academy of Sleep Medicine for the treatment of insomnia, it is nevertheless commonly used as a short term, over the counter treatment. It appears most useful in those who have trouble falling asleep as many studies have reported that it decreases sleep latency (i.e. time it takes to fall asleep). If you do take Benadryl for sleep, be sure to get a full 8 hours, otherwise next day sleepiness may occur. This is particularly common in the elderly.

The usual recommended dose of Benadryl for insomnia is:

Adults: 50 mg by mouth at bedtime as needed. 

Elderly: 25 mg by mouth at bedtime (although it is not considered a medication of choice)

Children 12 and Over: 50 mg by mouth at bedtime as needed. However, the FDA recommends against the use non-prescription products for sedation in children of any age.

Summary

To sum up, Benadryl helps you sleep because it can make you tired. It makes you tired because:

• It crosses the blood brain barrier, blocking histamine receptors in the brain. Newer antihistamines, such as Claritin and Allegra, do not cross the blood brain barrier and therefore are not associated with drowsiness.

• Benadryl has strong anticholinergic effects, which add to the sedation you feel.