Can You Take Melatonin with Benadryl?

The information in this article is for educational purposes only and should not be considered medical advice. [Read our full health disclaimer]

Updated on September 19, 2023

There are many things that keep us awake at night: the noise outside, the noise inside, getting over-sentimental while thinking about hedgehogs, raccoons, and koalas because their cuteness knows no limit, Chris from work who never shuts up about the covid jab he got and how you can avoid him tomorrow, whether Swans will make it to the AFL Grand Final this year, and so on.

When you go to a drugstore for a completely different reason and see all the over-the-counter sleep aids, these images and thoughts might come back to you multiplied. At the same time, all the melatonin supplements and sleeping pills such as Benadryl would try to seduce you with their promises of a good sleep and a good night – not a night you cannot forget, and nothing clandestine at all, but a night that you can easily forget because you will have no trouble sleeping.

The temptation might even be so strong that you might think of taking these over-the-counter medications together. Melatonin and Benadryl? Maybe a bit of valerian on top? Ambien or Unisom as an appetizer? But, before you start thinking about what to take for dessert, you should stop and ask whether taking melatonin with Benadryl is safe in the first place.

Lucky for you, I have the answer, and it’s a no. Before getting to why that is the answer, though, let’s see what melatonin and Benadryl are and how they work.

What Is Melatonin?

Melatonin is actually a hormone that’s produced by our pineal glands and that is already present in everybody. Among other things, its release works to ensure we get sleepy under low light like in the nighttime and to regulate a healthy sleep-wake cycle and circadian rhythm. Thanks to those attributes, it’s also an active ingredient of many sleep aids that you can find over-the-counter. These aids are not considered as drugs by many official drug administration organizations like the FDA, though, and they are labelled under the category of dietary supplements.

At this point, you might ask why people with sleep problems prefer taking melatonin supplements if it’s already produced by our bodies. The answer is simple: not every pineal gland is perfect and as a result, some people have low hormone levels. However, you should keep in mind that melatonin is not the only hormone responsible for us to have a healthy sleep and that melatonin shortage is not the only reason for sleep disorders. That is especially the case for older adults who suffer from chronic insomnia. According to the American Academy of Sleep Medicine, there is no evidence or research suggesting that it works or it’s safe, and unless you have a low level of melatonin in your body, its effectiveness won’t go further than a mild placebo effect.

But it’s not a completely useless supplement, either. People who have problems with circadian rhythm and those who have jet lag might benefit from it in the short term as it will have some sedative effects on them. Still, it’s my duty to remind you that these OTC supplements are not monitored as they are not prescription drugs, and not all of them may contain reliable ingredients.

What Is Benadryl?

Benadryl’s active ingredient is diphenhydramine, which is also one of the main ingredients in many over-the-counter drugs such as Tylenol and ZzzQuil, and Benadryl owes its fame to the sedating capabilities of diphenhydramine and is mostly used for treating allergic reactions.

Diphenhydramine actually belongs to the family of antihistamines alongside allergy drugs that contain doxylamine, and their working principles are the same: preventing the immune system and sometimes even the brain from producing more histamine. As histamine is a neurotransmitter responsible for giving your body and brain a sense of wakefulness, its release decreases when you are ready to sleep, and that’s how antihistamines result in sleepiness: by blocking the sense of wakefulness. In other words, your central nervous system slows down when you take one, and your brain is deceived to sleep.

Due to its powerful sedation, Bernadyl mostly works by reducing the sleep onset, thus making falling asleep easier. It’s possible that you are going to reap its benefits about an hour after taking it. But what about the rest of your sleep time and what about your sleep quality? Does easily falling asleep mean you’ll have better sleep?

Unless you get a good sleep of at least eight hours after taking Benadryl, you will wake up as if you have a hangover the next day and you’ll suffer from drowsiness during the course of the day. Also, the quality of your sleep will not be as good as a natural one and long-term use will result in more sleep disorders instead of taking care of one sleepless night.

What Happens When You Take Melatonin with Benadryl?

If we take the medical advice of the experts seriously, which we should, there is already enough suspicion about the effectiveness of these OTC sleep aids and concerns about the risks they might pose in the long term. However, a night or two when you don’t have time to consult with your doctor and are having a hard time falling asleep, you might consider taking them together, tempted to forget all the things that keep your eyes wide open. However, there are risks associated, including:

  • Over-sedation: Antihistamines slow the central nervous system down by blocking the production of histamines, which sedates your body and deceives your brain that it’s sleep time. An extra intake of melatonin creates a similar sense of sedation in the body. Taking both these supplements together might cause an over-depression of the nervous system, over-sedation, and extra grogginess the next day as if you didn’t even get any sleep.
  • Adverse effects on brain health: With both Benadryl and melatonin, you are basically interrupting the natural course of your body and deceiving your brain, but that’s not all. Benadryl also prevents acetylcholine from doing its job – a brain chemical that partially controls our attention span and short-term memory. Therefore, long-term use will inevitably cause dramatic changes to related brain functions, which might resurface later in your life from dreaded territories such as Alzheimer’s disease.
  • Short-term side effects: Not only when combined but also even when taken by themselves, these supplements are known to result in side effects that are the exact opposite of what you hoped for. For example, extreme drowsiness the next day, dry mouth, urinary retention, and constipation are some of the side effects of Benadryl. Melatonin, too, might lead to excessive daytime sleepiness as well as headaches. What good would be a drug-induced sleep after which you are still sleepy and drowsy?


Melatonin supplements are good for jet lag, and you might take Benadryl for allergic reactions come early spring with its abominable pollen infestation of our beautiful planet. And, you know what, okay, once or twice a month, when you really need to sleep badly and can’t, taking both together might also work (even though you might wake up less rested than before), but if you are experiencing sleep problems on a regular basis, that will not solve your problems in the long run – rather, you’ll start experiencing more problems and be causing possible damage to some crucial brain functions like attention and short-term memory. Therefore, it’s simply not recommended.

If you have regular sleep problems, the first course of action should be trying to adopt better sleep hygiene: turning off electronic devices an hour before bedtime, setting a sleep schedule, addressing issues like stress and anxiety, and seeing a specialist.

Bree Taylor - Lead Editor

Lead Editor

Bree is an interior designer with a passion for helping people improve their sleep quality.

She specializes in creating comfortable and functional bedroom spaces that promote a good night’s rest.

When she’s not testing mattresses or helping people get the best rest possible, Bree loves to travel and explore new cultures.

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