7 Natural Sleep Aids That Don’t Always Mix With Prescription Drugs

Sleep-boosting supplements are common, but they can be dangerous when taken alongside certain prescriptions

Cassandra Burns,

AARP

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Published March 11, 2026

light blue background features a sleep mask with gold eyelashes surrounded by various natural sleep aids, including St. John’s wort, valerian root, cannabis leaves, tart cherries, a spoonful of kava powder, and several white supplement pills

AARP (Getty Images,7)

As many as 70 million adults in the U.S. don’t sleep as well as they might like, and research suggests 1 in 5 takes some kind of sleep aid to help. Older adults are especially prone to sleep troubles, since sleep disorders become more common with age.

People often see supplements and herbal remedies as the first line of defense against poor sleep and for good reason. Having a cup of chamomile tea or a Sleepy Girl Mocktail before bed certainly seems easier than scheduling a doctor’s visit and starting a new medication. But it’s important to keep in mind that natural doesn’t always mean safe — especially if you are taking certain medications.

There are three categories of sleep aids: over-the-counter medications such as diphenhydramine (Benadryl), prescription drugs such as eszopiclone (Lunesta), and dietary supplements such as melatonin and magnesium.

When you pick up a new prescription, your pharmacist has likely already checked to make sure it won’t interact with any other medications you’re already taking. But you don’t get the same guidance when you buy a supplement online or off the shelf at a big-box store.

Supplements aren’t regulated by the Food and Drug Administration (FDA) in the same way that over-the-counter medications are, even though they, too, can come with side effects and drug interactions.

Here’s a look at seven popular natural sleep aids that can impact how prescription drugs work inside your body.

1. St. John’s wort

As a sleep aid, St. John’s wort is generally used to treat anxiety and depression as underlying disorders that contribute to sleeplessness. However, according to Daniel Malone, a research professor of pharmacotherapy at the University of Utah’s Skaggs College of Pharmacy, this supplement is also “a well-known inhibitor of an enzyme that affects a lot of medications.”

St. John’s wort can change how well certain drugs work, including some immunosuppressants, HIV medications, benzodiazepines, statins and drugs used to treat atrial fibrillation (AFib) and congestive heart failure. It can also interact with blood thinners, like warfarin, and certain cancer medications, including irinotecan, imatinib and docetaxel.

2. Melatonin

Melatonin use in the U.S. has skyrocketed in recent years. The number of adults taking the over-the-counter supplement more than quintupled between 1999 and 2018, a 2022 JAMA study found.

Dr. David Neubauer, a sleep‑medicine specialist and associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, explains that melatonin is a hormone that the body naturally produces to help trigger sleep. Taking a supplement can boost your natural levels, which may help you fall asleep faster.

However, Neubauer says that’s where the benefit stops. “Melatonin is not likely to help people stay asleep throughout the night,” he explains.

Melatonin has fewer drug interactions than other supplements, though Malone says it shouldn’t be combined with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, as well as tyrosine kinase inhibitors, which are a type of cancer medication.

What’s more, the National Institutes of Health’s (NIH) National Center for Complementary and Integrative Health says people with epilepsy and those taking blood-thinning medications should be under medical supervision when taking melatonin supplements.

It’s also important to know that what’s on the label might not match what’s in the bottle of melatonin supplements. In a 2023 JAMA study, a team of researchers found that 22 of the 25 products sampled contained significantly different amounts of melatonin than advertised.

3. Valerian root

People have been taking valerian root since the times of early Greece and Rome. Today, it’s promoted for insomnia, anxiety, stress and depression. However, experts aren’t exactly sure how, or even if, valerian root improves sleep. Trials treating insomnia with valerian root have been inconclusive.

What experts do know is that valerian root shouldn’t be taken alongside other sedatives, including benzodiazepines, central nervous system depressants and barbiturates. The NIH also cautions against taking valerian root alongside St. John’s wort, kava and melatonin.

4. Magnesium

Magnesium is a naturally occurring mineral that helps regulate muscle function, blood pressure and glucose levels. As one of the main ingredients in the viral Sleepy Girl Mocktail, magnesium continues to trend. But as for whether magnesium is effective for sleep, experts say the evidence is thin.

Magnesium may interact with diuretics, certain antibiotics, gabapentin, some HIV drugs, acid relievers and drugs used to treat osteoporosis, as well as zinc and calcium supplements. People with kidney problems should also speak with their doctors before taking magnesium.

5. Tart cherry juice

Tart cherry juice is the star ingredient of the aforementioned mocktail. This sour fruit has been linked to better sleep, though research published in Food Science & Nutrition says more studies are needed to fully understand whether tart cherry directly affects sleep.

Because it’s sour, most people don’t usually overdo tart cherry juice. However, it’s important to keep in mind that the drink contains quercetin, a plant compound that can interact with certain blood thinners and anticoagulants.

6. Cannabis

Cannabis has long been used for sleep, and unlike many natural sleep aids, its uses and effects on the body have been widely studied. Despite how sleepy you may feel after a THC gummy, long-term cannabis use may actually harm your sleep.

You shouldn’t take cannabis alongside other central nervous system depressants like alcohol or opioids because they can amplify its sedating effects. Cannabis can also interact with certain immunosuppressants, antiepileptics, benzodiazepines and antifungals.

7. Kava kava

Kava kava supplements are made from the roots of an herb found in the South Pacific. Some report its effects as relaxing and sedating, making it a viable sleep aid. However, kava has been banned in certain countries, and the FDA issued a warning for consumers in 2002, saying that kava supplements could be linked to severe liver injury.

Researchers found that kava has a high chance of interacting with prescription drugs that are metabolized by specific enzymes. Taking kava supplements could affect how your body processes SSRIs as well as substances known for affecting liver function, including alcohol.

Before you take a sleep aid, keep these six things in mind:

Don’t double up: Both Neubauer and Malone stress the importance of taking only one sleep aid at a time, unless otherwise directed by a physician. “Anything that’s going to induce sleep will interact with another medication that will induce sleep,” Malone says.

Be aware of different regulatory standards: Supplements, including those listed above, aren’t regulated by the FDA in the same way as prescription and over-the-counter medications. Supplements can include additives and multiple ingredients that may not be listed on the label.

Skip the nightcap: If you’re taking a sleep aid, Neubauer cautions against drinking alcohol before bed. Though it may initially have a sedating effect, alcohol can backfire and affect how well you sleep through the night. Malone notes that, as a general rule, people shouldn’t combine alcohol with medications or supplements.

Be careful with Benadryl: Many over-the-counter sleep aids and cold medicines include antihistamines, which Neubauer says can have cumulative and sedating effects when used with other medications. Neubauer adds that first-generation antihistamines, like Benadryl, can be especially risky for adults 65 and older, since they can cause confusion and falls.

Moderation is key: “Go slow, start low,” Malone says. Don’t exceed recommended dosages and talk to a clinician if your sleep doesn’t improve after taking any kind of aid, supplemental or otherwise.

Consider lifestyle tweaks: As people age, their circadian rhythms shift, and “there are natural changes in sleep patterns that people experience with aging,” Neubauer says.

After retirement, people may need to adjust their bedtimes and evening routines to better align with a changing sleep-wake cycle. “Regularity is key,” he adds. “Having a regular bedtime and morning rise time, you really can’t cheat that.”

Talk to your doctor or pharmacist

Physicians and pharmacists can help you decide whether or not to begin using a sleep aid, and they can guide you toward the best option for your personal needs. Providers can also check for drug interactions and may offer product advice too.

As for whether to stick with supplements or switch to prescription sleep aids, Neubauer says that “we’re in a golden age in terms of having safer medicines that represent a broad range of pharmacology” and that “we’re in a better position to customize personalized treatments.”

We’re also in a golden age of information, so use what’s available to you to make an informed decision and start catching some z’s.

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