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 Dec 14, 2017

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Dec 14, 2017
Benadryl Melatonin Together


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

While they work differently mechanistically, they have a similar effect. Use of both together could potentially cause excess sedation, disrupt the sleep cycle and create additional sleep disturbances when used at the same time.

While we will discuss both drugs in more detail below, the key point is this:

  • 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 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.[1]

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.[2][3]

A little known side effect of Benadryl is that it can sometimes cause a paradoxical reaction in people.[4]

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.

Section Summary
Benadryl is a 'first-generation' sedating antihistamine, used to prevent allergy symptoms and as a sleep aid.

How Melatonin Works

As mentioned above, melatonin works via a different mechanism than Benadryl.

The main difference between melatonin and Benadryl is that melatonin is an endogenous (i.e. 'natural') hormone that our bodies produce in the pineal gland.

The release of melatonin in our bodies is stimulated by darkness and suppressed by light and has a major role in our sleep-wake cycle and circadian rhythm.

To generalize, when we get ready to sleep, melatonin levels increase. When we are ready to get up, melatonin levels decrease.

Many studies show that melatonin supplementation is effective for certain situations that can lead to disruptions of the sleep-wake cycle such as with jet lag or in night shift workers.[5]

There is less evidence for benefit when used for short term treatment of insomnia. Nevertheless, there are studies that do show that melatonin can decrease sleep latency (i.e. time to fall asleep) and increase total sleep time, although the effects don't appear to be that profound.[6]

The most evidence of benefit for the use of melatonin may be in the elderly, or in those that have diminished melatonin levels.[7]

Section Summary
Melatonin is a naturally occurring hormone our bodies produce and has a variety of effects on the body, including regulating our sleep-wake cycle.

Taking Melatonin And Benadryl Together

Peaceful Woman Sleeping

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 taken 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.

Section Summary
Use of Benadryl and melatonin together on a regular basis is not recommended.
  1. ^ Elsevier ClinicalKey: Benadryl Monograph. ClinicalKey
  2. ^ Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. PubMed
  3. ^ Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety. PubMed
  4. ^ Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports. PubMed
  5. ^ Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews. PubMed
  6. ^ The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. PubMed
  7. ^ Improvement of sleep quality in elderly people by controlled-release melatonin. PubMed

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

Recent Questions