Taking Benadryl With Melatonin

In this article, our pharmacist discusses whether or not you can take Benadryl (diphenhydramine) and melatonin together.


Can you take Benadryl with melatonin?

Asked by Joe On Oct 13, 2021

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Oct 13, 2021
Last updated Mar 03, 2022

Key points

  • Melatonin is a naturally occurring hormone our bodies produce and has a variety of effects on the body, including regulating our sleep-wake cycle.
  • Use of Benadryl and melatonin together on a regular basis is not recommended.

In most cases, Benadryl (diphenhydramine) and melatonin should not be taken together.

There isn't necessarily a 'drug interaction' between them, but both can cause sedation, and using them together could have additive effects.

These additive effects could potentially cause excess sedation, dizziness, and even confusion in some individuals.

Additionally, and this is an important point, melatonin is generally used to restore your normal sleep-wake cycle, and studies show that Benadryl can disrupt it, especially with long-term use.

Now, using them together once in a while likely won't cause any harm, but again, long-term use should be avoided.

While I will discuss both drugs in more detail below, the key takeaways are:

  • The use of melatonin is most beneficial when you are trying to restore your normal sleep-wake cycle.
  • The use of Benadryl is known to cause changes to the normal sleep-wake cycle. The is in direct conflict with the use of melatonin. It is best for the short-term treatment of insomnia.

How Benadryl Works

Benadryl is a sedating, first-generation antihistamine.

It is well known to cause CNS (central nervous system) depression at usual doses of 25 mg to 50 mg.

Due to the sedative effects of the drug, it is very commonly used as an over-the-counter sleep aid. In fact, diphenhydramine (the active ingredient in Benadryl) is included in several OTC products, including ZzzQuil and Tylenol PM.

The onset of sedation is fairly quick, with maximum effects occurring 1 hour after administration.

The duration of action ranges based on the individual but generally lasts 4 to 8 hours.

When taking Benadryl as a sleep aid, it is important to get at least 8 hours of sleep, to reduce to risk of a 'hangover' effect.

Benadryl is well known to disrupt the sleep-wake cycle. Studies show that it can affect the time it takes to go to sleep, the amount of REM/non-REM sleep that occurs while you are sleep as well as the overall "feeling of rest" people experience.

A little-known side effect of Benadryl is that it can sometimes cause a paradoxical reaction in people.

Instead of causing sedation, a small number of people can experience excitation, nervousness, and restlessness. This is much more common in doses exceeding 25 mg and in children versus adults.

How Melatonin Works

Melatonin is a naturally occurring hormone produced by the pineal gland.

As a hormone, it has wide-ranging effects on the body, but it is most commonly known for its effects on our circadian rhythm and sleep patterns.

Melatonin is a very popular over-the-counter supplement. While it doesn't often make someone as drowsy as other over-the-counter sleep aids that are available, it can help individuals get better quality sleep over time.

Taking Melatonin And Benadryl Together

Although they work via different mechanisms, melatonin and Benadryl are not recommended to be taken together.

The use of both together can cause additive CNS depression and sedation.

Some studies also show that the combination can increase the risk of a next-day 'hangover' effect.

Lastly, both drugs have contradictory effects. Benadryl disrupts the sleep-wake cycle while melatonin promotes a return to a healthy sleep-wake cycle.

In general, Benadryl is best used intermittently to produce sedation for acute problems with insomnia.

Melatonin is best suited in those with low melatonin levels, or are in a situation in which their sleep-wake cycle is disrupted (e.g. due to jet lag or in night shift workers).

There are certainly some situations where taking both Benadryl and melatonin may be necessary (say for example you regularly take melatonin but need to use Benadryl to stem an allergic reaction), but be done consistently to help you sleep better.


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  • Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports., PubMed
  • Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews., PubMed
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  • Improvement of sleep quality in elderly people by controlled-release melatonin., PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 11 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication related questions!

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