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).

Conclusion

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). 


  1. MedlinePlus. (2020, Feb 18).v Diphenhydramine. Retrieved from https://medlineplus.gov/druginfo/meds/a682539.html
  2. Ibid. 
  3. Pharmotech SA. CBD Drug Interactions. Retrieved from https://pharmotech.ch/cbd-drug-interactions/
  4. Eileen Konieczny and Lauren Wilson. Healing with CBD: How Cannabidiol Can Transform Your Health without the High (California: Ulysses Press, 2018). P46-47.
  5. Grinspoon, P. (2018, Aug 24). Cannabidiol (CBD) — what we know and what we don’t. Retrieved from https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476.
  6. Sharkey KA, Darmani NA, Parker LA. Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Eur J Pharmacol. 2014;722:134–146. DOI:10.1016/j.ejphar.2013.09.068. 
  7. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18–041. doi:10.7812/TPP/18-041.
  8. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. DOI:10.4155/fmc.09.93.
  9. Vuolo F, Abreu SC, Michels M, et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur J Pharmacol. 2019;843:251–259. DOI:10.1016/j.ejphar.2018.11.029.
  10. Petrosino S et al. Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis. Journal of Pharmacology and Experimental Therapeutics June 2018, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368.
  11. Grinspoon, P. (2018, Aug 24). Cannabidiol (CBD) — what we know and what we don’t. Retrieved from https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476.
  12. Gray SL, Anderson ML, Dublin S, et al. Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study. JAMA Intern Med. 2015;175(3):401–407. doi:10.1001/jamainternmed.2014.7663. 
  13. Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49.
CBD Clinicals is reader-supported. When you buy through links on our site, we may earn an affiliate commission. Learn more

Featured Posts


Spruce CBD Review

Spruce is a family-owned business based out of Raleigh, North Carolina. The company was founded in 2018 in the belief that modern medicine is broken and that there is a need for alternatives to dangerous pharmaceuticals. Spruce’s lab-grade CBD oil is 100% natural and tested by a third-party lab in...

Read more

Best CBD Oil for High Blood Pressure (Hypertension)

Why People Are Taking CBD for High Blood Pressure? According to the Centers for Disease Control and Prevention (CDC), high blood pressure can harden the arteries, which decreases the flow of blood and oxygen to the heart, leading to heart disease(5). In a 2015 study conducted by researchers from the...

Read more

NuLeaf Naturals Review

Based in Colorado, USA, and founded in 2014, NuLeaf Naturals is one of America’s top pioneering hemp companies. NuLeaf Naturals wellness products are derived from specially bred therapeutic hemp (Cannabis Sativa) plants grown on licensed farms in Colorado. Their hemp CBD plants are 100% organic whole-plant extracts and grown with...

Read more

Best CBD for Neuropathy (Nerve Pain)

As medical cannabis products have become more popular, people are turning to them to treat everything from anxiety to depression to chronic pain. Individuals who are suffering from neuropathy may show interest in trying CBD oil. What Is CBD? CBD comes from a plant that is part of the Cannabaceae...

Read more

SabaiDee Review + Discount Coupon Code for 2020

SabaiDee CBD products are tested both in-house and by independent laboratories to verify the quality of every batch. Their products all come with SabaiDee’s Happiness Guarantee. 

Read more

Top 4 Best CBD Oil for Dogs With Cancer

Why Some People are Using CBD for Dogs with Cancer? An article posted by the American Kennel Club (AKC) says that there is no conclusive scientific data on using cannabidiol (CBD) to treat dogs specifically. However, there is anecdotal evidence from dog owners suggesting that CBD can help with neuropathic...

Read more

CBD Oil for Kids with Anxiety

Why People are Turning to CBD for Children with Anxiety? CBD has become a popular OTC treatment that parents give their children, says Doris Trauner, M.D., professor of neurosciences and pediatrics at the University of California San Diego School of Medicine and a physician at San Diego’s Rady Children’s Hospital....

Read more

CBD Oil for Candida

Why People are Turning to CBD for Candida? Candidiasis or thrush is a medical condition caused by Candida albicans, a yeast-like fungus. This type of fungus spreads over within the mouth and throat, and it usually infects men and women alike. Certain cannabinoids, like CBD, have been shown as a...

Read more