CBD and Warfarin - CBD Clinicals (original) (raw)

Does CBD interact with warfarin?

• Warfarin is predominantly metabolized by the cytochrome P450 (CYP450) system. CBD inhibits enzymes that belong to this class(1).
• A 2017 case report by the U.S. National Library of Medicine National Institutes of Health explained that CBD competes in a similar metabolic pathway with that of warfarin(2).
• Taking warfarin together with CBD can make warfarin stay in the body for too long without being broken down. This may have detrimental effects such as excessive bleeding, or worse, overdose(3).
• Patients who intend to use CBD with warfarin must seek the advice of a licensed medical professional first to ensure that the drug interactions will not be dangerous to their health.

Can CBD Be Taken with Warfarin?

It is not recommended to take CBD with warfarin.

Warfarin (brand names: Coumadin, Jantoven) is an oral anticoagulant or blood thinner that is primarily used to help prevent and treat blood clots. It can also be administered to treat blood clots arising from certain heart conditions, heart attack, or open-heart surgery(4).

Warfarin is metabolized by Cytochrome P450, also known as CYP450. It is a class of liver enzymes that play an essential role in the metabolism of warfarin and other medications before the drugs are cleared through the renal system(5).

CYP450 includes CYP3A4, CYP1A1, CYP2C8, CYP1A2, CYP2C18, CYP219, and CYP2C69, which predominantly metabolize warfarin(6).

Consequently, medications, treatments, and other factors that affect the CYP269 enzyme can also alter the effects of warfarin in the body(7).

Like warfarin, CBD is metabolized through the hepatic P450 enzyme system. Both CBD and warfarin share similar proteins during their respective metabolism processes.

CBD is metabolized by the body through CYP1A1, CYP1A2, CYP2C19, CYP3A4, CYP2D6, CYP269, and CYP3A5, five of which are active enzymes that act on warfarin.

A 2017 study facilitated by the U.S. National Library of Medicine National Institutes of Health explained that CBD competes in a similar metabolic pathway with that of warfarin(8).

CBD also acted as a powerful inhibitor of CYP3A4 enzymes, which can diminish the degradation of warfarin(9). This is also known as the “grapefruit effect” as the grapefruit juice can also slow down the body’s absorption of warfarin(10).

As such, taking warfarin together with CBD can make warfarin stay in the body for too long without being broken down. This may have detrimental effects such as bleeding, or worse, overdose(11).

This is why regular measurement of a user’s international normalized ratio (INR) is necessary, more so when warfarin is taken with CBD. It ensures that the blood levels remain within a narrow range to avoid the side effects brought by warfarin.

Mayo Clinic presented a number of warfarin side effects that require immediate medical attention(12):

• Excessive bleeding, including heavy menstrual bleeding, nosebleed, and internal hemorrhage
• Bloody or black stool
• Brown or red urine
• Reduced urine output
• Bruises that appear even without suffering from any injury
• Chronic pain in the stomach
• Headache
• Vomiting of blood
• Changes in the vision
• Unusual weakness, tiredness, or dizziness
• Joint pain, swelling or discomfort, especially after experiencing an injury
• Stupor

Other less serious side effects of warfarin are:

• Bleeding between menstruation period
• Gum bleeding after brushing the teeth
• Vomiting, diarrhea, or being unable to eat for 24 hours or more
• Fever

In rare cases, warfarin can also cause necrosis or death of skin tissue. Any changes in skin temperature or color, as well as severe pain on the skin, warrant prompt medical care. Be on the lookout for blotchy, net-like spots on the skin, too.

Pain in the toes, especially when they turn dark or purple in color, signifies a severe health problem.

Patients who intend to use CBD with warfarin must seek the advice of a licensed medical professional first to ensure that the drug interactions will be beneficial to their health.

Can Another Oral Anticoagulant Be a Substitute for Warfarin so CBD Oil Can Be Taken?

Among the remaining three oral anticoagulants approved by the FDA to treat irregular rapid heart rate, two are also metabolized by the CYP450 system. Thus, they can also be subjected to the grapefruit effect of CBD(13).

These oral anticoagulants are rivaroxaban and apixaban(14).

Meanwhile, a 2011 review explained that another approved oral anticoagulant, dabigatran (Pradaxa), does not undergo metabolism through CYP450. According to the review, dabigatran has shown a few drug-food and drug-drug interactions. Medical professionals are also considering dabigatran as a substitute for warfarin therapy(15).

However, it is still best to schedule a consultation with a health professional before taking any anticoagulant along with CBD to ascertain safety and body tolerance.

The U.S. Food and Drug Administration or FDA has authorized the use of warfarin for the following purposes:

• Treat clots that form in the vein (venous thrombosis) and associated pulmonary embolisms or blood clot in the lungs(16)
• Treat thromboembolic complications caused by cardiac valve replacement or irregular or rapid heart rate (atrial fibrillation)(17)
• Reduce the risk of death, recurrent heart attack or myocardial infarction (MI) and other thromboembolic events such as stroke and systemic embolism that may occur after a cardiac arrest(18)

Can CBD Replace Warfarin?

There is no specific study or case report that directly expounds on CBD as a safe substitute for warfarin or any anticoagulants.

One study used an obese rat model to describe how cannabis extract could possibly contain anticoagulant effects is that of a 2007 study written in the journal Phytomedicine(19_)_.

The study showed that cannabinoids such as cannabinol (CBN) and tetrahydrocannabinol (THC) demonstrated anticoagulant activity(20).

Thus, the authors suggested that Cannabis sativa and the cannabinoids THC and CBN can be potentially used to treat thrombosis and type 2 diabetes, a kind of ailment which could cause an irregular increase of blood clotting(21).

Since there are limited studies on whether CBD can act as an anticoagulant, it is still best to ask a medical expert before considering CBD as a replacement for a prescription drug, and there is currently no evidence to suggest that CBD could be anticoagulant medications.

What to Look for in a CBD Product

There are several things to keep in mind before purchasing CBD products, the first of which is seeking a doctor’s approval. Once it is done, consider these action steps prior to buying any CBD product.

1. Check the laws in the area where the product will be bought and consumed. In the United States, there are jurisdictions that have specific restrictions regarding the allowable THC content in CBD products.
2. Take time to read reviews before buying from an online store. When buying from a clinic or a physical store, make sure that it is an authorized CBD seller by the government. Remember to purchase from reliable and legitimate brands only.
3. Examine the additional ingredients. Some products include beneficial ingredients like MCT oils or melatonin. However, there are also CBD products that contain potentially dangerous ingredients such as vegetable glycerin and propylene.
4. Determine the right dosage. CBD intake may be low dose or higher depending on the user’s condition.

It is advisable to talk to a trusted and experienced medical professional who has deep knowledge about CBD to minimize probable risks and avoid side effects, especially because CBD has other verified drug interactions, too.

Studies show that aside from warfarin, CBD also inhibits the metabolism of other drugs, including clobazam, an anti-epileptic medicine(22).

The grapefruit effect also applies to certain kinds of benzodiazepines, a class of prescribed medications for anxiety. Some of the benzodiazepines that are metabolized by the CYP450 system are alprazolam (Xanax), brotizolam, triazolam, and midazolam(23).

An author and professor of medicine at Harvard Medical School, Peter Grinspoon, MD, warns the public through a Harvard Health article that CBD can cause nausea, irritability, and fatigue(24).

In addition, Brent A. Bauer, M.D., medical editor of Mayo Clinic Book of Alternative Medicine, also explained that other side effects of CBD include diarrhea, reduced appetite, dry mouth, fatigue, and drowsiness(25).

What food, supplements, and drugs interact with warfarin?

Warfarin, like other medications, can interact with vitamins, nutritional supplements, drugs, and food. The interaction might lessen the efficacy of warfarin or increase the risk of bleeding.

Aside from grapefruit, some of the typical food and drinks that can interact with warfarin are:

• Garlic
• Alcohol
• Cranberry juice or cranberries
• Pomegranate
• Black licorice

Common herbal or nutritional supplements that might interact with warfarin include:

• Dong Quai
• Ginseng
• Coenzyme Q10 (ubiquinone)
• Green tea
• St. John’s wort
• Vitamin E

Some of the common drugs that have been identified to have warfarin interaction include:

• Laxatives or antacids
• Aspirin or any product that has aspirin
• Antifungal medications like fluconazole (Diflucan)
• Acetaminophen or any product that has acetaminophen
• Several antibiotics
• Allergy or cold medicines
• Naproxen sodium (Naprelan, Aleve) or ibuprofen (Motrin IB, Advil)
• Medications used to treat abnormal heart rhythms (Nexterone, Pacerone)

Some of the medical conditions that can also increase the risk of bleeding are:

• Uncontrolled blood pressure
• Stomach ulcer, peptic disease or gastritis
• Cancer
• Alcoholism
• Kidney ailments
• Liver disease
• Increased risk of falling
• Stroke history

The presence of the following ailments may affect the usage of warfarin:

• Catheter insertion
• Congestive heart failure
• Anemia
• Diabetes
• High blood pressure or hypertension
• Kidney disease
• Blood disease called Polycythemia vera
• Deficiency in Protein C
• Thrombocytopenia (heparin-induced)
• Bowel problems or stomach ache including bleeding
• Inflammation of blood vessel (vasculitis)
• Spinal anesthesia
• Intestinal or stomach ulcer
• Threatened miscarriage (patients who have this condition are strictly discouraged from taking warfarin)
• Deficiency in Vitamin K
• Malnutrition
• Fats in the stool or steatorrhea
• Diarrhea
• Trauma

How to Minimize the Risk of Bleeding while Taking Warfarin

There are action steps that can be taken to lower the risk of bleeding while undergoing warfarin treatment:

• Inform the attending physician of all the medications and supplements that a patient is taking. Doing so can help the doctor evaluate if further testing or dosage adjustment is needed, or if a new drug might alter the effect of the warfarin treatment.
• Be cautious of injury, especially from falling. As much as possible, abstain from participating in contact sports that may cause bruising or physical damage. Report any chronic pain in case an injury occurred.
• Keep away from sharp objects to avoid being cut.
• Refrain from nose-picking and, if needed, gently blow the nose.
• If a patient who is having warfarin treatment undergo surgeries or even minor procedures like dental cleanings or vaccinations, tell the assigned health care provider about it to ensure proper and safe medical attention.
• Use a soft-bristled toothbrush, electric razor, and waxed dental floss for hygiene and grooming. Ask the physician for a safer way to clean the gums and teeth.
• In case of emergency, it will be helpful if a patient has a card or note that says he is having warfarin treatment (and other medications, if any) so the medical providers can take the right course of action.

Understanding the Role of Vitamin K with Warfarin Treatment

Vitamin K is a nutrient that can lessen the effectiveness of warfarin. However, it is vital for the heart and bones. Consistency in Vitamin K intake is necessary when taking warfarin. A sudden increase in Vitamin K consumption can significantly increase clotting risk.

The recommended Vitamin K intake level for adult men and women is 120 micrograms (mcg) and 90 mcg, respectively.

Food and drinks that are rich in Vitamin K include:

• Spinach
• Kale
• Collards
• Chard
• Mustard greens
• Turnip greens
• Broccoli
• Asparagus
• Plums
• Asparagus
• Rhubarb
• Green tea
• Brussels sprouts
• Certain oils extracted from vegetables such as soybean oil and canola oil

Before making any changes in the diet, it is encouraged to consult a physician for proper guidance.

Conclusion

Cannabidiol or CBD is one of the chemical compounds found in the cannabis plant. It is a non-psychoactive substance, which means it will not make a person “high”. The body reacts to cannabinoids through the receptors in the endocannabinoid system.

Since CBD is absorbed by the body through the CPY450 system, which is also responsible for the metabolism of warfarin in the body, it is not recommended to take CBD and warfarin together. Doing so may cause the warfarin to stay longer in the body than necessary and may lead to harmful effects such as excessive bleeding and overdose.

Expert medical advice is highly encouraged before consuming CBD products either as a replacement for a prescribed drug or a nutritional supplement.

1. Yamaori S., Ebisawa J., Okushima Y., Yamamoto I., Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011;88(15–16):730–736

2. Yamaori S., Koeda K., Kushihara M., Hada Y., Yamamoto I., Watanabe K. Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab Pharmacokinet. 2012;27(3):294–300.

3. Deaton, J. G., & Nappe, T. M. (n.d.). Warfarin Toxicity. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK431112/

4. Mayo Clinic. (2020, February 1) Warfarin (Oral Route) Retrieved from: https://www.mayoclinic.org/drugs-supplements/warfarin-oral-route/description/drg-20070945

5. Lynch T, Price A. The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects. Am Fam Physician. 2007 Aug 1;76(3):391-396. Retrieved from https://www.aafp.org/afp/2007/0801/p391.html

6. Coumadin Product Data- FDA. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789126/

7. Johnson J.A. Clinical pharmacogenetics implementation consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017 (n/a-n/a); Whirl-Carrillo M., EMM, Hebert J.M., Gong L., Sangkuhl K., Thorn C.F. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92(4):414–417; Wadelius M., Chen L.Y., Downes K., Ghori J., Hunt S., Eriksson N. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. J Pharm. 2005;5(4):262–270. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789126/

8. Yamaori and Koeda, op. cit.

9. Yamaori and Okushima, op. cit.

10. Grinspoon, P. (2019, Aug 27). 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.

11. Deaton, J. G., & Nappe, T. M. (n.d.). Warfarin Toxicity. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK431112/

12. Mayo Clinic. Warfarin Side Effects: Watch for Interactions. Retrieved from https://www.mayoclinic.org/diseases-conditions/deep-vein-thrombosis/in-depth/warfarin-side-effects/art-20047592

13. Doliner B, Jaller JA, Lopez AJ, Lev-Tov H. Treatments to prevent primary venous ulceration after deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2019 Mar;7(2):260-271.e1.

14. W., M., D., K., & M., B. (2013). Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. doi: 10.1111/bcp.12075.

15. Ganetsky, M., Babu, K. M., Salhanick, S. D., Brown, R. S., & Boyer, E. W. (2011). Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant, 7(4). doi: 10.1007/s13181-011-0178-y

16. Sharp CR, deLaforcade AM, Koenigshof AM, Lynch AM, Thomason JM. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 4-Refining and monitoring antithrombotic therapies. J Vet Emerg Crit Care (San Antonio). 2019 Jan;29(1):75-87.

17. Badjatiya A, Rao SV. Advances in Antiplatelet and Anticoagulant Therapies for NSTE-ACS. Curr Cardiol Rep. 2019 Jan 12;21(1):3.

18. Unger, E. F. (2015, October 16). Atrial fibrillation and new oral anticoagulant drugs. Retrieved from https://www.fda.gov/drugs/news-events-human-drugs/atrial-fibrillation-and-new-oral-anticoagulant-drugs

19. Coetzee, C., Levendal, R. A., van de Venter, M., & Frost, C. L. (2007). Anticoagulant effects of a Cannabis extract in an obese rat model. Phytomedicine, 14(5). doi: 10.1016/j.phymed.2006.02.004

20. ibid.

21. ibid.

22. Anderson, L. L., Absalom, N. L., Abelev, S. V., Low, I. K., Doohan, P. T., Martin, L. J., … Arnold, J. C. (2019). Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions. Epilepsia, 60(11). doi: 10.1111/epi.16355.

23. Otani, K. Cytochrome P450 3A4 and Benzodiazepines. Seishin Shinkeigaku Zasshi. 2003;105(5):631-42. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12875231

24. Grinspoon, P. (2019, Aug 27). 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.

25. Bauer, B. A. (n.d.). What are the benefits of CBD — and is it safe to use? Retrieved from https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700

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