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Blood Thinners and CBD Oil Interaction

Blood Thinners and CBD Oil Interaction

CBD oil is showing signs of being an effective anticoagulant, but is it safe to combine with traditional blood thinners?

CBD oil is making headlines for its use in treating hypertension and heart disease, so naturally, if you suffer from a hemostasis disorder, you may be wondering if CBD could be of any help in treating your condition.

Although CBD oil has been shown to be relatively safe, it should be used cautiously with some blood thinning medications, including one of the most commonly prescribed anticoagulants.

If you are considering combining CBD oil and blood thinners, or simply want to discover if it’s a safe option, here is everything you need to know.

Effects of CBD on Blood Clotting

The effects that CBD oil has on blood clotting are not well understood, but it is thought that a few factors come into play. First, is CBD oil’s impact on blood flow.

CBD oil can aid the circulatory system by dilating blood vessels. This allows the blood to flow quicker, and in turn, can make the occurrence of blood clots less likely. A 2017 study found that just a single dose of CBD significantly reduced the blood pressure of subjects at rest and in stressful situations.

Broad- or full-spectrum CBD oil in particular may be a useful tool in preventing thrombosis, or the formation of blood clots. A study on the anticoagulant effects of cannabis found the cannabinoids (tetrahydrocannabinol) THC and cannabinol (CBN) to be effective anti-thrombotics, doubling the amount of time it took for blood clots to form in obese and lean rat test subjects compared to the control group.

Both CBN and THC are present in full-spectrum CBD oil, which contains all of the hemp plant’s cannabinoids and terpenes. Full-spectrum CBD oils will typically have 0.3% THC or less, which is in line with federal regulations. If you’d rather not have THC in your CBD product, but still are after the anticoagulant effects of CBN and CBD, a broad-spectrum CBD oil is the way to go. Broad-spectrum CBD products contain all the cannabinoids and terpenes of the hemp plant except THC. If you aren’t sure whether you’d like a full- or broad-spectrum product, a good place to start is researching your state’s laws on cannabis, THC, and CBD.

Interactions Between CBD and Blood Thinners

Although CBD oil has been found to be generally well-tolerated and free from side-effects, it can interact negatively with some pharmaceuticals. Often referred to as the ‘grapefruit effect,’ CBD oil is one of a number of natural substances that can slow down the system the body uses to process toxins.

This system is known as the cytochrome P-450 enzyme system, and is made up of liver enzymes that break down certain medications into smaller parts so your body can more easily process them. When the P-450 enzyme system is inhibited by a compound like CBD, other medications typically broken down by those liver enzymes remain in the system for longer than is desired, making it more likely that you will experience the side effects of that unprocessed medication.

As you’ll see in the table below, not all pharmaceuticals are processed by the cytochrome P-450 enzyme system. So while you may need to take care when combining CBD oil with a blood thinner like Warfarin, for example, users of Heparin face fewer risks.

Ultimately, it’s important to consult with your doctor before using CBD oil if you take any blood thinning medication. This will allow your doctor to make adjustments to your medication, taking into account any changes that CBD oil may have in its processing time.

As a starting point, here is a list of some of the most commonly prescribed blood thinners and what we currently know about their interaction with CBD oil.

Anticoagulant Type Brand Name Common Drug Side Effects Possible Side Effects of Combining Medication + CBD Oil
Rivaroxaban Xarelto Prolonged bleeding; bruising easily; nosebleeds; bleeding gums Rivaroxaban may remain in the system longer and increase the likelihood you’ll experience its side effects
Dabigatran Pradaxa Prolonged bleeding; bruising easily; nosebleeds; bleeding gums No known interaction
Apixaban Eliquis Prolonged bleeding; bruising easily; nosebleeds; bleeding gums Combine with caution; apixaban may remain in the system longer and make side effects more likely
Edoxaban Lixiana Prolonged bleeding; bruising easily; skin rash; reduced liver function; anemia No known interaction
Warfarin Coumadin; Jantoven Unusual bruising; bleeding gums; nosebleeds; prolonged bleeding Combine with caution; Warfarin may remain in the system longer and side effects could become more likely
Heparin Various Prolonged bleeding; bruising easily; nosebleeds; bleeding gums; skin irritation; allergic reaction No known interaction

How to Safely Take CBD and Blood Thinners Together

When combining CBD oil and blood thinners, there are a variety of factors that come into play. Your health, weight, and general tolerance can all influence how likely you are to experience interactions. Because there are so many variables to consider, you should first speak to your doctor about the possibility of adding CBD oil to your medication regimen. Together you can create a plan to ensure there is minimal disruption to your system.

In order to further minimize the risks of an adverse reaction between CBD oil and your anticoagulant, it’s suggested that you start with a lower dose than what is recommended for your chosen CBD product, and slowly increase the dosage over time if needed. This not only allows you to build a tolerance to CBD oil, but it also provides your doctor with the time and flexibility to decrease the dosage of your blood thinners if required.

Safest CBD Oils to Take with Blood Thinners

With so many varieties of CBD oil available to you, how do you know where to start? If you’re looking for a safe CBD oil to combine with blood thinners, or are turning to CBD oil as a preventative measure against blood clots, there are a few things to consider to ensure you’re making the smartest and safest purchase possible.

First, choose your CBD delivery method. You can buy CBD oil in a wide number of forms including capsules, vapes, edibles, and drops. While vaping CBD will deliver the fastest results, drops are more discreet with longer-lasting effects, and capsules offer a user-friendly, familiar option for people who are new to CBD. When deciding on a method it is worth noting that any format that’s processed through the digestive system will take longer to show effects and as such may lose some of its potency.

After you have chosen the preferred method for your CBD delivery, look for a high quality CBD product that has been organically grown, sustainably sourced, and third-party lab tested. Reading the lab reports, also called Certificates of Analysis, will ensure the product you purchase is in fact the safest CBD oil to take with blood thinners. A Certificate of Analysis should tell you if the CBD product you’ve contains herbicides, pesticides, heavy metals, or chemical additives.

When you have your CBD oil product, figuring out your ideal dosage is the last step to making sure you’re using CBD safely. The safest way to take CBD oil with blood thinners is to start with a small dose and increase gradually over a period of time if needed. For additional personal guidance on CBD dosage, consider speaking with a naturopathic doctor who specializes in using CBD oil to treat medical conditions.

If you’ve spoken to your physician and are ready to choose a CBD oil, check out the Best CBD Oil Products to Buy.

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Learn the risks, benefits, and possible side effects of taking CBD oil while on blood thinner medication.

An interaction between warfarin and cannabidiol, a case report

Leslie Grayson

a University of Alabama at Birmingham, United States

Brannon Vines

a University of Alabama at Birmingham, United States

Kate Nichol

b Greenwich Biosciences, United States

Jerzy P. Szaflarski

a University of Alabama at Birmingham, United States

Highlights

  • • An interaction between warfarin and cannabidiol is described
  • • The mechanisms of cannabidiol and warfarin metabolism are reviewed
  • • Mechanism of the interaction is proposed
  • • INR should be monitored in patients when cannabinoids are introduced

1. Introduction

The use of cannabis products for the treatment of epilepsy and other chronic diseases is growing rapidly [1], [2]. Cannabis products include any pharmaceutical or artisanal derivatives of the cannabis plant [2]. One such agent is cannabidiol (CBD), one of the phytocannabinoids frequently used by patients with seizures. Current data regarding interactions between CBD and other pharmaceuticals are primarily limited to anti-seizure drugs [3], [4]. This case report observes a clinically significant interaction between pharmaceutical grade cannabidiol (Epidiolex®; Greenwich Biosciences, Inc.) and warfarin, one of the most widely used oral anticoagulants.

2. Case report

A 44-year-old Caucasian male with Marfan Syndrome, mechanical mitral valve replacement, warfarin therapy, and post-stroke epilepsy was enrolled in the University of Alabama at Birmingham open-label program for compassionate use of cannabidiol for the management of treatment-resistant epilepsy ( > NCT02700412). His seizures began at age 27 concurrent with diagnosis of stroke during the post-operative period from cardiac surgery. Despite initial control of seizures on monotherapy, events returned in 2011 prompting adjustment of anti-seizure medications and eventual consideration of epilepsy surgery. Following video EEG monitoring, he was determined to be a poor surgical candidate due to non-localized seizure onset. Additionally, the need for anticoagulation due to mechanical valve limited more invasive testing for localization of seizure focus as well as posed a challenge for completion of any surgical resection. He was subsequently referred to the UAB CBD program.

At the time of study enrolment, the patient was taking lamotrigine 400 mg and levetiracetam 1500 mg, both twice daily. He was also taking warfarin 7.5 mg daily with a goal International Normalized Ratio (INR) of 2–3. Prior to study entry, his INR had been stable for at least 6 months with levels ranging from 2.0 to 2.6 ( Fig. 1 ). At the initial study visit, his baseline INR was obtained and he was placed on the starting dose of CBD at 5 mg/kg/day divided twice daily. Per study protocol (www.uab.edu/cbd) CBD dose was increased in 5 mg/kg/day increments every two weeks.

INR Trend over time.

With up-titration of CBD oil, a non-linear increase in the INR was noted ( Table 1 , Fig. 1 ). Warfarin dosage adjustments were made by primary care physician in effort to maintain an INR within his therapeutic range. At the most recent study visit his warfarin dose had been reduced by approximately 30%. The patient was followed clinically without bleeding complications.

Table 1

Visit # Day # Date Weight (kg) CBD dose (mg/kg/day) CBD dose (mg BID) Coumadin dose averaged over time between visits (mg) INR
1 0 10/29/15 105.9 0 0 7.5 2.22
2 14 11/12/15 105.9 5 265 7.5 2.96
3 28 11/23/15 105.5 10 528 7.5 6.86
4 42 12/10/15 105.5 15 790 5.89 4.40
5 70 1/07/16 104.8 15 786 6.25 2.8
6 84 1/21/16 105.8 20 1058 6.78 3.27
7 98 2/04/16 108.2 25 1352 6.78 4.07
8 126 3/03/16 107 20 1070 6.51 2.73
9 140 3/17/16 106.8 25 1335 6.42 3.93
10 168 4/14/16 107.1 25 1338 6.07 3.49
11 238 6/23/16 105.1 25 1313 5.36 1.96
12 252 7/07/16 104.6 30 1570 5.36 2.6
13 266 7/21/16 105.7 30 1585 5.36 2.25
14 294 8/18/16 104.1 30 1562 5.36 2.41
15 322 9/15/16 104.8 35 1834 5.36 2.31
16 336 9/29/16 105.5 40 2110 5.36 2.90
17 364 10/27/16 106.9 35 1870 5.36 2.80
18 434 1/05/17 107.2 35 1876 5.36 2.88
19 518 3/30/17 103 35 1802 5.36 2.58

3. Discussion

Despite the emergence of novel oral anticoagulants, warfarin continues to be the most commonly used oral anticoagulant worldwide [5]. A potent inhibitor of vitamin K epoxide reductase complex, warfarin functions by disrupting the production of vitamin-K-dependent clotting factors [6]. The drug is comprised of R and S stereoisomers with S-warfarin being the more active of the two. Warfarin is metabolized via the CYP450 hepatic enzyme complex and cleared through the renal system, however each stereoisomer is metabolized differently. The S-isomer is predominantly metabolized by CYP2C9 and R-warfarin by way of CYP3A4 with lesser involvement of CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18 and CYP2C19 [6]. Resultantly, factors that impact the CYP2C9 enzyme (genetic polymorphisms, other medications, etc.) alter warfarin activity [5], [7], [8]. Due to its narrow therapeutic index and variability of dosing requirements amongst individuals, frequent monitoring of the INR is required to both achieve and maintain appropriate anticoagulant effects on the blood. Drugs that compete as substrates for these cytochromes or inhibit their activity may increase warfarin plasma concentrations and INR, potentially increasing the risk of bleeding. Conversely, drugs which induce these metabolic pathways may decrease warfarin plasma concentrations and INR, potentially leading to reduced efficacy.

The metabolism of CBD is also by way of the hepatic P450 enzyme system. To date there are seven major isoforms identified that contribute to this process: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5, with CYP3A4 and CYP2C19 being the dominant contributors [9]. Five of the seven isoforms are also involved with metabolism of warfarin, including CYP2C9, which is the dominant enzyme for S-warfarin, and CYP3A4, which is the dominant enzyme for R-warfarin [7], [9]. In addition to competing for enzymes in same metabolic pathway as warfarin, CBD has been demonstrated to act as a potent competitive inhibitor of all seven of its own CYP enzymes and as such could further impair the degradation of warfarin [10], [11]. It is this combination of factors that presumably constitutes the observed rise in INR values with concomitant warfarin and CBD administration.

4. Conclusions

This finding suggests an interaction between warfarin and cannabidiol, underscoring the importance of monitoring appropriate laboratory work in patients receiving concomitant cannabis products and other pharmaceuticals, particularly those metabolized by the cytochrome P450 enzyme system. In patients taking warfarin, INR monitoring is suggested during initiation and up-titration of cannabinoids.

An interaction between warfarin and cannabidiol, a case report Leslie Grayson a University of Alabama at Birmingham, United States Brannon Vines a University of Alabama at Birmingham,