The pharmacist discusses whether or not it is safe to take CBD (cannabidiol) with Benadryl (diphenhydramine). Due to how Benadryl is metabolized, the concentrations of the drug could remain at peak levels for a longer period of time when taken with CBD. Learn more. CBD Drug Interactions: Does CBD interact with antihistamines like diphenhydramine? Learn more about the two drugs and their moderately significant interaction.
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.
CBD Oil and Benadryl – August 2022
Does CBD interact with Benadryl and other antihistamines?
Benadryl is the brand name for a substance known as diphenhydramine HCL. Diphenhydramine belongs to a class of medications called antihistamines. It can alleviate human allergy symptoms, but people also commonly use Benadryl for dogs experiencing allergic reactions.
Antihistamines work by blocking the activity of histamine, a substance in the body that causes allergic symptoms (1 ) .
Diphenhydramine is used to alleviate symptoms, like red, itchy, irritated, and watery eyes, sneezing, and runny nose caused by allergies, hay fever, or the common cold.
Diphenhydramine is also used to relieve coughs caused by minor throat or airway irritation. Moreover, diphenhydramine is used to prevent and treat motion sickness, and to treat insomnia (difficulty falling asleep or staying asleep) (2 ) .
Can CBD Be Taken With Benadryl?
There is no known interaction between CBD (cannabidiol) and Benadryl. However, there is a potential risk when combining CBD and Benadryl, as both are metabolized (broken down) through the cytochrome P450 enzyme system.
Due to how Benadryl is metabolized, the concentrations of the drug could remain at peak levels for a longer period of time when taken with CBD.
The CYP450 liver enzymes are responsible for metabolizing potentially toxic compounds, including over 60% of any over-the-counter or prescription drugs consumed.
Certain substances can affect processing times within this system, making drugs metabolize faster or slower than they would on their own.
Cannabidiol can inhibit the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times (3 ) .
Antihistamines use the cytochrome P450 enzyme system and can interact with CBD, as reiterated by authors Eileen Konieczny, RN, and Lauren Wilson, in their book, Healing with CBD (4 ) .
According to an article written in August 2019 by Peter Grinspoon, MD, any medicine can have different effects on different people.
For example, Benadryl, an antihistamine, makes some people sleepy yet can make others wide awake. Thus, it is not inconsistent for a particular medicine to cause a symptom in one person and to help alleviate it in another (5 ) .
Until studies that specifically look at how CBD interacts with Benadryl are completed, talk with a doctor to make sure that there are no CBD drug interactions with other medications currently taken.
Can CBD Replace Benadryl?
There is no scientific study that recommends using CBD as a substitute for Benadryl. However, studies have shown that CBD possesses therapeutic characteristics that may help with symptoms of medical conditions for which Benadryl is indicated.
These conditions include nausea, insomnia, mucus production, minor throat or airway irritation, and inflammation.
A review from the European Journal of Pharmacology established the potential of cannabis to limit or prevent nausea and vomiting from a wide range of causes (6 ) . Results also demonstrated the crucial role of cannabinoids and their receptors in the regulation of nausea and vomiting.
A study from January 2019 looked at the role of CBD in anxiety and sleep, showing a positive correlation. The results, published in The Permanente Journal , indicated that individuals with anxiety or poor sleep experienced an improvement in both or either cases when taking CBD every day (7 ) .
CBD has been shown to interact with the endocannabinoid system to reduce mucus production, as one review in Future Medicinal Chemistry indicated (8 ) .
In another 2019 study , which was published in the European Journal of Pharmacology , scientists found that CBD helped to reduce airway inflammation and fibrosis in animal subjects that were experiencing an allergic asthmatic response (9 ) .
Meanwhile, CBD’s potent anti-inflammatory properties were demonstrated in a 2018 study published in the Journal of Pharmacology and Experimental Therapeutics (10 ) . CBD may also be useful in treating different types of chronic pain according to a study on the animal model for arthritis (11 ) .
Benadryl has been used for many common symptoms and medical conditions. However, as with most pharmaceuticals, Benadryl use comes with side effects and health risks.
In a 2015 report published in JAMA Internal Medicine, researchers offered compelling evidence of a link between long-term use of Benadryl and dementia (12 ) .
Meanwhile, studies have shown that CBD possesses therapeutic characteristics that may help with symptoms of medical conditions that Benadryl addresses.
However, no scientific study recommends using CBD or any CBD products with Benadryl. Neither is there a study that promotes CBD as a substitute for Benadryl.
While CBD is generally safe, as the 2011 review in the Current Drug Safety Journal suggests, the long-term effects are yet to be examined further (13 ) .
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.