Can you mix melatonin and Benadryl for sleep?

If you’re desperate for sleep, you might be willing to try anything.

But before you overdo it on sleep supplements, it’s important to know which medications are safe to take together---and which aren’t. Melatonin and Benadryl are both common, over-the-counter meds used by many to support deeper sleep. On their own, each is a relatively mild option for short-term sleep support.

But if you’re thinking of doubling down in hopes of increasing your chances of catching some ZZZs, it’s best to do your research first. Here’s everything you need to know about mixing melatonin and Benadryl. 

Understanding the common culprits of disturbed sleep is a good place to start, as different sleep issues can benefit from different treatments. Here are the most frequent sources of sleep problems:

Your lifestyle and diet affect everything in your life, including the quality of your sleep.

When it comes to what you consume, having too much caffeine or consuming caffeine too late in the day can disrupt sleep---that’s no secret. But what and when you eat can also affect sleep quality; poor dietary habits or too much food before bed can keep you up. On the other hand, going to bed without enough sustenance or on an empty stomach might mean waking up from hunger.

Sometimes, your sleep issues are as simple as revamping your daily habits. For example, a lack of exposure to sunlight can negatively impact your circadian rhythm, as can jet lag or erratic work schedules. Some prescription medications can also interfere with sleep. This includes drugs like alpha and beta-blockers which treat high blood pressure, antidepressants like selective serotonin-reuptake inhibitors (SSRIs), cholesterol medication, and corticosteroids used for conditions like asthma, lupus, and rheumatoid arthritis. While you should never stop taking medication without speaking to your health care provider, if you think your prescription is causing you to skimp on shut-eye, it’s worth mentioning to see if there’s a better medication for you.

Healthy sleeping habits are critical. Excessive stimulation before sleep---the kind you might experience by watching TV, exercising, playing video games, or using your computer or phone too close to bedtime---can inhibit natural melatonin production, resulting in less restful shuteye. Your sleeping environment also plays a large role: if you have a space that’s uncomfortable, noisy, or exposed to light, you might find yourself unable to sleep through the night.

And while the occasional nap is okay, regularly catching up on missed sleep by snoozing during the day can also get tricky. Naps that are too long can result in sleep issues at night and lead to general fatigue.

Specific sleep disorders like sleep apnea, insomnia, restless legs syndrome, and delayed sleep phase disorder can have significant effects on sleep quality and duration. But non sleep-specific conditions like anxiety, depression, and chronic pain can also interfere with or prevent slumber.

Even nutrient deficiencies play a role. Research published in Public Health Nutrition found that there is a link between sleep duration and magnesium, iron, and zinc levels in the body. The quality of sleep can also be affected if certain nutrient levels are too high, such as vitamin B12, copper, and potassium.

Melatonin is a hormone produced by the brain whose primary job is to help us fall and stay asleep. It’s involved with regulating your circadian sleep-wake cycle, and the body is supposed to release it at night as bedtime approaches.

However, our modern lifestyles do a lot to get in the way of healthy melatonin production: nighttime lights and screen usage, irregular sleep patterns, inadequate sun exposure, and stimulating activities (like work or exercise) before bed can all disrupt the release of melatonin. Most people take melatonin supplements because they are seeking a more natural remedy for insomnia and sleep issues, and studies demonstrate that it can support increased sleep duration and quality while causing fewer side effects than non-natural sleep aids (provided you are taking the appropriate dosage, of course).

Melatonin supplementation also has other potential benefits, including:

But be aware: low melatonin levels can affect other hormones like vitamin D and cortisol, so simply adding a melatonin supplement to your routine could mask other problems.

Technically, sleepiness is a side effect of Benadryl rather than the actual purpose. This fatigue is caused by Benadryl’s primary active ingredient, diphenhydramine, which is an antihistamine intended to relieve allergies, hay fever, and colds. It’s actually known as a “drowsy” antihistamine (as opposed to “non-drowsy”) because of its sleep-inducing effects.

Benadryl’s active ingredient is what’s added to most non-prescription sleep aids, including Tylenol PM and Advil PM, to give them slumber-inducing effects. So if you’re taking a name-brand like Tylenol PM or Advil PM simply in order to sleep, generic diphenhydramine would have the same effect. It’s important to note, however, that the American Academy of Sleep Medicine (AASM) does not recommend using diphenhydramine as a means to fall and stay asleep. This is based on weak evidence of its efficacy in improving sleep onset and total sleep time.

Though Benadryl has many known drug interactions, none are associated with taking melatonin and Benadryl at the same time. While we don’t have any studies saying it’s unsafe to mix the two, that doesn’t mean it’s a suitable sleep solution in the long-term.

Even melatonin supplements, which are safe for most adults, should typically only be taken for short-term sleep disturbances. Interestingly, over time, melatonin may make other prescribed medications less effective. Research has also found that melatonin’s efficacy is inconsistent at best. This is due to a few factors, including the drug’s short half-life, the amount of time it takes melatonin to reduce by half in your system. Since the recommended amount on the average bottle of melatonin to take is so small, there are debates on whether or not it’s enough to impact sleep. However, taking larger doses without guidance from a doctor isn’t advised, since you risk side effects like daytime sleepiness and headaches. That’s why the AASM recommends against treating chronic sleep disorders like insomnia with over-the-counter medications like Benadryl and herbal supplements like melatonin. There’s not enough evidence that they are effective and safe for long-term use.

Finding a remedy for your sleep issues (especially a long-term solution) involves identifying and addressing the root cause rather than trying to reverse or mask the symptoms.

If the disturbance seems potentially related to your lifestyle or sleeping habits, then it’s not a bad idea to start there to make behavioral changes that will support better sleep. Even if that isn’t the cause, it’ll only lead to positive outcomes. You might take a look at your caffeine and sugar intake, your nighttime routines, your sleeping environment, bedtime screen exposure, and other factors to see what adjustments can be made to support more restful nights.

However, if you suspect that something less visible might be the culprit, Base’s personalized at-home lab service offers an option specifically for sleep testing. This easy-to-use kit can uncover what might be missing in your nutrient, hormone, and vitamin levels to cause insomnia or fatigue.

Here’s how this can help: once you know what’s missing, you can make specific lifestyle or supplement adjustments to help regulate your sleep-wake cycle. Base will analyze your results to offer personalized recommendations tailored to your body’s needs. In the long term, this can help you find sustainable sleep solutions without guesswork or band-aids.

If you’re looking for a quick fix---for example, something that will help you recover from a slightly-thrown-off sleep schedule---then taking melatonin and/or Benadryl could offer what you need. Just keep in mind that even though there are no adverse interactions from taking melatonin and Benadryl together, it’s best to heed the advice of the American Academy of Sleep Medicine (AASM) and steer clear from regular melatonin and Benadryl use when it comes to trying to solve your sleep issues.

Instead, find a long-term solution by addressing any underlying issues that may be caused by a hormonal imbalance, or nutrient and vitamin deficiencies. Make an appointment with your health care provider for a blood test or consider a personalized, at-home service like Base. With Base you’ll get ongoing health data and recommendations that can help you achieve quality shuteye… without constantly reaching for sleep aids.