The pharmacist discusses whether or not it is safe to take CBD (cannabidiol) with Benadryl (diphenhydramine). CBD Drug Interactions: Does CBD interact with antihistamines like diphenhydramine? Learn more about the two drugs and their moderately significant interaction. In our latest question and answer, the pharmacist discusses whether or not it is safe to take Benadryl and CBD together.
Taking CBD (Cannabidiol) With Benadryl
The pharmacist discusses whether or not it is safe to take CBD (cannabidiol) with Benadryl (diphenhydramine).
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.
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.
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:
- Multiple Sclerosis
- Parkinson’s Disease
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:
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.
Does CBD Interact With Diphenhydramine (Benadryl)?
Information on risks & possible interactions between CBD & diphenhydramine (Benadryl).
Diphenhydramine (DPH) is the active ingredient in the anti-allergy medication Benadryl and sleep aid Unisom.
Taking diphenhydramine with CBD (cannabidiol) can result in moderate to severe drug interaction. CBD increases the severity of the side effects of diphenhydramine while also decreasing its clearance from the system.
These two agents should not be taken together unless instructed by a physician.
Table of Contents
Does CBD Interact With Diphenhydramine (Benadryl)?
Yes, CBD can increase blood levels of diphenhydramine (Benadryl) over time, leading to severe side effects.
Diphenhydramine is a fast-acting and readily available medication. Due to its action on the histamine receptors, the medication can produce several side effects: confusion, drowsiness, dizziness, and sedation.
CBD may inhibit the breakdown and excretion of diphenhydramine from the body, leading to elevated levels of this medication in the bloodstream. High serum blood levels of diphenhydramine are extremely dangerous.
1. Increased Effects (Agonistic Interaction)
This type of interaction refers to the increased activity or effects caused by the drug after it interacts with CBD.
CBD and other cannabinoids may enhance the sedative effects of diphenhydramine, causing severe sedation and sleepiness. This interaction is uncomfortable but can also be dangerous. Users may fall asleep suddenly while driving or operating other forms of machinery — potentially leading to injury or death.
Additionally, this level of sedation could interfere with essential responsibilities, such as monitoring small children or pets.
2. Slowed Elimination (Metabolic Competition)
Medications need to be excreted out of the system after they have produced their effects.
Drugs are excreted through urine or feces, a process that requires the metabolism of the drug first. Drug metabolism is usually the function of the liver. Almost 90 percent of all medications metabolize in the liver; it uses different enzymes and enzyme systems such as Cytochrome CYP450.
Enzyme CYP2D6 mainly metabolizes diphenhydramine . It also metabolizes CBD, which could inhibit or slow the breakdown of diphenhydramine .
Over time, diphenhydramine could accumulate in the body, leading to dangerously high levels. People who use it daily are most at risk of this interaction.
If you use diphenhydramine every once in a while, it’s unlikely this interaction will be a significant concern. However, if you’re using it daily or in high doses, this interaction could lead to severe side effects, including delirium, sedation, or even death.
Other Names for Diphenhydramine
Diphenhydramine is sold under many different names. All share the same risk and potential interactions.
Other names for diphenhydramine include:
CBD & Other Antihistamines
Diphenhydramine is classified as an antihistamine. CBD and antihistamines all share similar risks for interaction and side effects.
Here’s a list of similar medications that share an equal level of risk when combined with CBD:
- Carbinoxamine (Palgic)
- Desloratadine (Clarinex)
- Hydroxyzine (Atarax & Vistaril)
- Levocetirizine (Xyzal)
- Brompheniramine (Dimetane)
- Cetirizine (Zyrtec)
- Chlorpheniramine (Chlor-Trimeton)
- Clemastine (Tavist)
- Diphenhydramine (Benadryl)
- Fexofenadine (Allegra)
- Loratadine (Alavert & Claritin)
Is It Safe to Take CBD & Diphenhydramine Together?
No, CBD and diphenhydramine (Benadryl) are not safe to take together unless specified by a physician.
It’s important to avoid their interaction unless medically necessary.
Before combining these compounds, it’s crucial to weigh the benefits and the possible drug interaction to ensure maximal health benefits.
Is CBD a Viable Alternative to Benadryl?
No, CBD has entirely different effects and is not an alternative for diphenhydramine.
With that said, CBD does offer some mild anti-allergy benefits in the form of anti-inflammatory effects . CBD is also a mild to moderate sedative that may provide support in place of diphenhydramine (Unisom) for improving sleep.
For seasonal allergies, CBD can offer direct benefits in the form of its inhibitory action on pro-inflammatory cytokines . Once exposed to an allergen, the human body secretes pro-inflammatory cytokines that cause what we refer to as seasonal allergy symptoms.
These benefits take a while to work. You’re not going to be able to wake up in the morning feeling stuffy and take some CBD to clear it up. Diphenhydramine is much better for acute allergies.
However, if you know you have seasonal allergies, CBD may work as a preventative if taken consistently during allergy season.
What Is Diphenhydramine (Benadryl)?
Benadryl is the brand name for a compound called diphenhydramine (DPH). It’s an antihistamine drug and works by blocking the histamine receptors to relieve allergy symptoms, hay fever, and the common cold, such as itching, watery eyes, runny nose, and a sore throat.
Diphenhydramine is the key ingredient of Benadryl and is also available under different brand names like Unisom and Nytol. Regardless of the brand name, the chemical structure used remains the same. The medication dosage and the form, tablet, capsule, rapid dissolving pills, or syrup, differ for patients based on their age group and primary complaint.
Diphenhydramine (Benadryl) Specs:
|Trade Name||Benadryl, Sominex, Banophen, Nytol, & Unisom|
|Classification||Anticholinergic antiemetics, Anticholinergic antiparkinson agents, Antihistamines, Miscellaneous anxiolytics, and sedatives and hypnotics|
|CYP Metabolism||Liver (CYP2D6, CYP1A2, CYP2C9, and CYP2C19)|
|Interaction with CBD||Agonistic (Increased effects) & Metabolic Inhibition|
|Risk of Interaction||Moderate to Severe (With Long-Term Use)|
What Does Diphenhydramine Do?
Diphenhydramine (Benadryl) targets the histamine receptors, namely H1R. These receptors are in the respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons.
The activation of H1R results in vasodilation, causing flushing and smooth muscle contractions like bronchospasms, laryngospasms, and coughing. It also stimulates the entry of neutrophils to the affected area, which is important for developing symptoms of an allergic reaction.
Diphenhydramine inhibits the H1R as an inverse agonist, meaning that it binds to the receptor’s active site where histamine would normally bind. It also inhibits the receptor, producing effects opposite to the usual effects of H1R.
Diphenhydramine belongs to the first generation antihistamines, and the main difference between first-generation and second-generation is that the former can cause drowsiness and even act as a sedative. This is because diphenhydramine and other first-generation antihistamines can cross the blood-brain barrier and act as an inverse agonist on the H1R in the brain.
Diphenhydramine is also antimuscarinic; it targets muscarinic acetylcholine M2 receptors because M2 receptors and H1 receptors are structurally similar. This antimuscarinic action of diphenhydramine on acetylcholine receptors makes the medication a potential antiparkinson medication. Parkinson’s is a disorder that alters the balance between acetylcholine and dopamine in the brain.
Diphenhydramine also is believed to affect the intracellular sodium channels, blocking their actions and producing an anesthetic effect.
What Are the Side Effects of Diphenhydramine (Benadryl)?
Diphenhydramine (Benadryl) is a potent medication with several uses and benefits. Similarly, there are quite a few risks and complications associated with diphenhydramine use, especially if taken in combination with other medicines.
- Dry mouth, nose, and throat
- Increased chest congestion
- Loss of appetite
When to Avoid Using Diphenhydramine (Benadryl)
Diphenhydramine (Benadryl) is an over-the-counter medication readily available to anyone with allergies or the common cold.
However, its use is not recommended for all age groups, especially older people. People over the age of 65 should only use the medication in case of a severe allergic reaction and after consulting with their primary care physicians.
Pregnant and breastfeeding women should refrain from using this medication. If used while pregnant, the person should inform their doctor immediately.
Moreover, it’s essential to avoid driving or operating heavy machinery after taking diphenhydramine as the medication is a strong sedative and can cause drowsiness. Mixing it with certain other drugs, such as other first-generation antihistamines and CBD, intensifies this drowsiness.
Key Takeaways: Is It Safe to Take Diphenhydramine With CBD?
Diphenhydramine (Benadryl) and CBD are both readily available in the United States without a prescription, but these two medications should not be used in combination — especially if taking diphenhydramine regularly.
Over time, DPH could build up in the bloodstream, leading to toxic levels. Side effects of this medication when serum levels increase can be severe — including delirium, severe somnolescence, memory loss, and death.
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.
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.
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.
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.