Benadryl And CBD Oil Interaction


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In our latest question and answer, the pharmacist discusses whether or not it is safe to take Benadryl and CBD together. The pharmacist discusses whether or not it is safe to take CBD (cannabidiol) with Benadryl (diphenhydramine).

Is It Safe To Take Benadryl And CBD Oil Together?

In our latest question and answer, the pharmacist discusses whether or not it is safe to take Benadryl and CBD together.

Audie asked

I just took 50mg of Benadryl and 30mg CBD oil to help me sleep. Now I’m nervous if this is safe. I didn’t even think about it when I took them. Is this safe?

At a glance

  • Combining CBD (cannabidiol) and Benadryl (diphenhydramine) cause result in additive sedation, drowsiness and dizziness. Taking them together during the day could impair your ability to concentrate and complete tasks that require concentration, like driving. Taking them together before bed likely shouldn’t cause any significant issues.


We touched on this topic a few years ago, but it’s always a good idea to go back and re-evaluate such topics in case any new information has come to light.

This is especially true for potential drug interactions concerning CBD (cannabidiol) as it has just exploded in popularity (and use) quite recently.

Not only has the over the counter (OTC) use of CBD skyrocketed, it is now available as a prescription product, Epidiolex, which is indicated for the treatment of rare seizure disorders.

After reviewing available information for Benadryl and CBD respectively, there doesn’t appear to be any changes to what we wrote about previously. that there is no specific drug interaction that we know of, but they should still be used cautiously since both can cause sedation, drowsiness, and dizziness.

More Detail

Our very own drug interaction checker (PharmacistAnswers Drug Interactions), which utilizes the DrugBank database, states the following regarding combining CBD and Benadryl:

Cannabidiols are capable of causing adverse effects such as dizziness, confusion, sedation, somnolence, and others to varying degrees. The concomitant use of cannabidiols with central nervous system depressants that can cause similar kinds of adverse effects can subsequently additively increase the risk, incidence, and/or severity of central nervous system depression for patients. PA Drug Interaction Checker

Benadryl (diphenhydramine) is a commonly used over the counter first-generation antihistamine. It does have ‘central nervous system depressant’ effects, which is why it is often used as a sleep aid. it makes you tired and drowsy.

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The risk here of using CBD and Benadryl together is the additive (i.e. combined) central nervous system depressant effects. In other words, you may feel these effects more pronouncedly.

The good news is that really dangerous CNS depressant effects, like shallow breathing and respiratory arrest, aren’t known to happen on these drugs (unlike other drug combos like benzodiazepines and opioids).

The prescribing information for Epidiolex, which again is a prescription CBD product that often calls for very high doses (hundreds to thousands of milligrams per day) only states the following regarding the interaction with CNS depressants:

CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on EPIDIOLEX to gauge whether it adversely affects their ability to drive or operate machinery. Epidiolex Prescribing Information

All in all, if you are just combining CBD and Benadryl at night, you shouldn’t have much of an issue. just the additive drowsiness as discussed.

Taking CBD (Cannabidiol) With Benadryl

The pharmacist discusses whether or not it is safe to take CBD (cannabidiol) with Benadryl (diphenhydramine).

Nate asked

Is it safe to take CBD oil with Benadryl? I want to make sure they don’t interact with one another.


There is no known interaction between CBD (cannabidiol) and Benadryl.

However, depending on the individual, CBD can cause sedation. Benadryl is a first generation antihistamine that is known to cause pronounced sedation.

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Therefore, there is a potential risk when combining both CBD and Benadryl in regard to the additive sedation that could occur. Nevertheless, there are no reported or documented interactions between CBD and Benadryl and the combination appears safe to take.

Below, we discuss CBD, Benadryl and a potential interaction in more detail.

CBD (Cannabidiol)

Cannabidiol, also known as CBD, is a major component of cannabis (i.e. marijuana). While THC (delta-9-tetrahydrocannabinol) is likely more well-known due to its psychoactive effects, CBD makes up almost 40% of cannabis extracts and has a wide range of effects and potential benefits when used medicinally.

Perhaps the biggest draw of CBD is the fact that it does not appear to impair mental functioning or cause euphoria. In fact, when combined with THC, it may counteract the sedative and psychoactive effects of THC.

CBD has been studied, and may provide benefit for a wide range of indications including:

  • Anxiety
  • Dystonia
  • Pain
  • Seizures
  • Multiple Sclerosis
  • Insomnia
  • Parkinson’s Disease
Benadryl (Diphenhydramine)

Benadryl (diphenhydramine) is a first generation antihistamine, which are noted for their relatively short duration of action (~4 to 8 hours) and their sedating properties.

In addition to its use for treating seasonal allergy symptoms such as a runny nose, Benadryl is also effective for treating symptoms of nausea, vomiting, and vertigo associated with motion sickness.

As Benadryl has fairly significant sedating effects, it is often used as a night time sleep aide and is a common component of over the counter sleep products such as ZzzQuil.

CBD Drug Interactions

Over the counter and medicinal CBD products have recently exploded in popularity. However, there is a distinct lack of studies when it comes to potential drug interactions between CBD and prescription/OTC medication, including Benadryl.

Preliminary studies indicate that CBD is known to be metabolized by the cytochrome P450 system. Specifically, studies have shown that CBD can inhibit the following metabolizing enzymes:

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When a metabolizing enzyme is inhibited, it can lead to increased concentrations of drugs that are typical substrates for that particular enzyme.

Benadryl Interaction With CBD

Benadryl (diphenhydramine) is known to be metabolized mainly by CYP2D6 but is also metabolized, to a lesser extent, by CYP1A2, CYP2C9, and CYP2C19.

Due to how Benadryl is metabolized, the concentrations of the drug could potentially be increased when taken with CBD.

However, there are a number of studies that theorize that while CBD does inhibit metabolizing enzymes, it is not significant and the blood concentrations needed to affect these metabolizing enzymes in humans far exceeds what is possible with usual dosing.

Many studies use doses in the range of 100mg to 600mg, well above what would be consumed by the average individual. It is possible the more commonly used low doses of CBD don’t have significant effects on metabolizing enzymes.

In regard to the potential of additive sedation, the effects of CBD are thought to vary greatly by individual and by the specific product that you are using. It appears that different varieties of CBD products contain significantly different amounts and types of terpenes. For example, one particular terpene, myrcene, may have more sedative effects than others.

Therefore, while some CBD products may cause sedation in individuals, other products could potentially increase alertness and focus.

Overall, until studies are completed that specifically look at how CBD interacts with Benadryl (diphenhydramine), we can only make educated guesses. It does appear that while there could potentially be additive sedation when combining CBD and Benadryl, the risk of any serious side effect appears low.

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