Previously, the skeptical cardiologist described a patient with atrial fibrillation who was taking the blood thinner apixaban (Eliquis ) and developed a nose bleed after consuming a large amount of grapefruit (see here.) In researching the whole subject of grapefruit-drug interactions I came across a fascinating intellectual battle between David Bailey, the researcher who first… Yes. CBD inhibits the cytochrome P450 enzyme, which is involved in metabolizing many drugs. Compounds in grapefruit inhibit the same enzyme group, which is why physicians advice patients not to eat grapefruit shortly before or after taking a medication. By inhibiting cytochrome P450, CBD can either reduce or increase the effects of other drugs. What Drugs Shouldn’t Be Taken with CBD? CBD, or cannabidiol, has become incredibly popular in recent years. After the production of industrial hemp was legalized in the United States, CBD
How Important Are Grapefruit (OR CBD Oil)-drug Interactions? David Bailey vs The Florida Dept. of Citrus
Previously, the skeptical cardiologist described a patient with atrial fibrillation who was taking the blood thinner apixaban (Eliquis ) and developed a nose bleed after consuming a large amount of grapefruit (see here.)
In researching the whole subject of grapefruit-drug interactions I came across a fascinating intellectual battle between David Bailey, the researcher who first identified a significant grapefruit-drug interaction, and clinicians and researchers, some of whom are supported by the Florida Citrus Board, who feel this interaction is not significant.
What Does The Internet Tell Us?
It’s always interesting to see what patients doing a Google search will see on important medical topics. When I Googled “grapefruit Eliquis interaction” I saw the following:
The first item is an ad from the company that makes Eliquis which takes you to their patient-oriented Eliquis site and immediately presents you with important patient safety information. Nowhere on the site is the word grapefruit listed (as of July, 2018).
The second item is what Google calls a snippet and which they will present to you as what they think is the best answer to your Google search question. In this case the snippet (and the first 4 hits) is lifted from Web MD an absolutely unreliable source of information (see my post on entitled Web Md:Purveyor of bad health information and snake oil) but one which Google (and thus millions of unsuspecting Googlers) relies on for answers to medical questions . Web MD advises you to avoid grapefruit if you’re taking eliquis.
Close inspection of the WebMD article proffering this advice reveals the sole reference that actually bears on this topic: (Bailey et al , 2012 , CMAJ).
The main author of this paper (which has the oddly phrased title Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? ) is David Bailey.
David Bailey: Rapid Runner and Grapefruit Alarmist
David Bailey may be better known as the first Canadian to run a mile in under 4 minutes. His Wikipedia entry spends equal time on his running career and on his major claim to fame: grapefruit drug interactions (GDI).
Bailey serendipitously discovered that grapefruit increased levels of the antihypertensive drug felodipine in his own body in 1987, information which was pretty much ignored until he published a research paper in the Lancet in 1991 showing a doubling of felodipine levels in 6 volunteers who consumed grapefruit.
Since then studies have shown that grapefruit juice acts by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall.
Bailey has taken the grapefruit (and Seville orange) ball and run with it. His publications emphasize the broad scope and potential dangers of multiple grapefruit-drug interactions. A 2012 Bailey paper lists 85 drugs with the potential to interact with grapefruit juice including, you guessed it, apixaban.
Despite these potential interactions the actual number of clinically significant interactions or harm reported is minuscule. This has not deterred Bailey from emphasizing the importance of the interaction he discovered.
He is quoted in a 2012 NY Times article as saying:
“The bottom line is that even if the frequency is low, the consequences can be dire,” he said. “Why do we have to have a body count before we make changes?”
“For 43 of the 85 drugs now on the list, consumption with grapefruit can be life-threatening, “
Articles, like the NY Times article typically buy into Bailey’s fear-mongering and spend multiple paragraphs describing a single case report suggesting that ingestion of grapefruit juice was responsible for a dangerous interaction but such cases are rare and strong evidence that grapefruit juice was responsible is not present.
What Can We Learn From The Florida Department of Citrus?
In fact, in a letter to the editor in response to Bailey’s 2012 review, two researchers point out that their is little solid evidence to suggest that the grapefruit-drug interactions are important
We know of no validated evidence that coadministration of grapefruit juice with a drug has caused a dangerous interaction, resulting in serious adverse effects or actual harm to a patient’s health. We point readers to 2 extensive review articles on grapefruit juice–drug interactions that have appeared in peer-reviewed medical literature. 2 , 3 These articles provide a review of primary research literature, a compilation of the extent of interactions with specific drugs, and an evaluation of their clinical importance; however, neither of these publications is cited in the CMAJ article.
Whereas David Bailey has a bias to promote and exaggerate an interaction that is his claim to scientific fame most of the research and reviews that counter his claims come from researchers who are likely heavily biased to minimize the importance of the interaction: they are funded by the Florida Department of Citrus.
Are We Missing Important Grapefruit Medication Interactions?
David Bailey would like us to believe that the GFDI he identified in 1998 is hugely important. If only doctors would spend more time investigating the grapefruit consumption of their patients we would realize this. He writes
But how big a problem are such interactions? Unless health care professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient’s diet, it is very unlikely that they will investigate it. In addition, the patient may not volunteer this information. Thus, we contend that there remains a lack of knowledge about this interaction in the general health care community. Consequently, current data are not available to provide an absolute or even approximate number representing the true incidence of grapefruit–drug interactions in routine practiceThe chemicals in grapefruit involved in this interaction are the furanocoumarins. 7
Bailey, goes on to warn us that all forms of grapefruit consumption can lead to dangerous interactions and other citrus fruits are to be feared as well
Because these chemicals are innate to grapefruit, all forms of the fruit (freshly squeezed juice, frozen concentrate and whole fruit) have the potential to reduce the activity of CYP3A4. One whole grapefruit or 200 mL of grapefruit juice is sufficient to cause clinically relevant increased systemic drug concentration and subsequent adverse effects. 11 , 12 Seville oranges, (often used in marmalades), limes and pomelos also produce this interaction. 13 – 15 Varieties of sweet orange, such as navel or valencia, do not contain furanocoumarins and do not produce this interaction. 2
You can follow his references but they are not to patients who were harmed by grapefruit-drug interactions. Indeed, I am unaware of any of my patients reporting such harm until my patient with the nose bleed. I tend to agree with this unbiased editorial from BMJ in 2013
In our experience, and in that of our experienced colleagues, we have yet to come across clinically meaningful interactions of drugs and GFJ. This is despite our day to day experience of managing patients on statins, calcium channel antagonists, anti-platelet agents and anti-arrhythmics, which covers over 10,000 patients in the last 10 years alone. Likewise, there is little formal evidence of an impact, even from large scale clinical trials, with adjudicated and well documented endpoints.
After considerable research and communication with Pfizer, the maker of Eliquis, I ended up agreeing with Pfizer’s conclusion that the grapefruit-Eliquis interaction was unlikely to be significant:
When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4. Therefore a dose adjustment of apixaban is not expected to be required.
CBD Oil, Grapefruit And Drug Interactions
I was reminded of the grapefruit-drug interaction in the last few weeks as several of my patients have started using CBD oil for various problems and have asked if it is safe to use with their cardiac medications.
I haven’t fully researched the CBD oil-drug interaction but the top Google search (“grapefruit and CBD oil”) result (from CBD school) states the following:
CBD interacts with other medications in your body in the same way as grapefruit, only even stronger.
However, the site that CBD school references (Project CBD) is not that definitive about grapefruit-drug interactions being a guide to CBD-grapefruit interactions.
And a recent scholarly article on the topic (see here) concludes
The drug-drug interactions between cannabinoids and various drugs at the CYP level are reported, but their clinical relevance remains unclear.
Which sounds very similar to where we are at with grapefruit-drug interactions in general.
I had my patient perform an experiment to see if the grapefruit actually caused her nose bleed. She repeated her consumption of large amounts of grapefruit and had no nosebleed this time.
Does CBD interact with other medications?
Yes. CBD inhibits the cytochrome P450 enzyme, which is involved in metabolizing many drugs. Compounds in grapefruit inhibit the same enzyme group, which is why physicians advice patients not to eat grapefruit shortly before or after taking a medication. By inhibiting cytochrome P450 , CBD can either reduce or increase the effects of other drugs. In some situations, it may be advisable for a physician to monitor a patient’s blood levels of other medications while taking CBD . See CBD -Drug Interactions: The Role of Cytochrome P450 for more information.
What Drugs Shouldn’t Be Taken with CBD?
CBD, or cannabidiol, has become incredibly popular in recent years. After the production of industrial hemp was legalized in the United States, CBD products became readily available in big box stores and even local pharmacies. But how do you know that it is safe for you to take CBD?
CBD is one of many naturally occurring compounds — known as cannabinoids — found in the cannabis plant. Like anything else that you may ingest, CBD has the potential to interact with other medications, supplements and substances. That is why it is critical to consult with your doctor before adding anything new to your diet.
Research on how CBD interacts with particular drugs is still ongoing. A good rule of thumb when it comes to CBD is to avoid taking it if your medicine has a “grapefruit warning.” If your doctor does give the green light for you to use CBD, be sure to shop for high quality products through a trusted source — such as Green Wellness Life.
How CBD May Interact with Certain Drugs
When you ingest any substance, whether it is a prescription medication, street drug, supplement, over-the-counter medicine, or alcohol, your body must metabolize it. This is the process of breaking down the substance. Drug metabolism happens throughout the body, but primarily occurs in the liver.
Our body makes specific enzymes, cytochrome P450 (CYP450) that convert foreign substances so that they can be eliminated from the body. Certain medications or substances may affect CYP450, by slowing down or speeding up the metabolism of drugs. This can change how your body processes medications, supplements, and other substances.
CYP450 is a broader term for a group of enzymes responsible for metabolizing drugs and other substances. The enzyme CYP3A4 is responsible for metalizing several cannabinoids, including CBD. When CYP34A processes CBD, it may interfere with the enzyme’s ability to process other substances.
This is important because CYP34A is responsible for metabolizing approximately 60% of the medications that we take. When CBD inhibits the work of this enzyme, it may not be able to effectively metabolize other medications. Similarly, many medications inhibit CYP34A, making it more difficult for your body to process CBD.
The end result is that medications — or CBD — may not work in the way that they are supposed to, or produce the intended result. If the medication is metabolized too slowly, it may remain in your system for longer than it should, causing side effects. If it is metabolized too quickly, then it may not have a chance to work properly. This is known as a drug interaction.
Which Drugs May Interact with CBD?
Research is still ongoing on how CBD may affect certain drugs. Several studies on the interaction between certain epilepsy medications and CBD found that CBD may increase the levels of clobazam and desmethlyclobazam in patients’ bodies. If you are on any anti-epileptic medication, check with your doctor about whether it is safe to take CBD.
One method that you may use to avoid an interaction between CBD and your medications is to avoid CBD if your medicine has what is known as a “grapefruit warning.” Consuming grapefruit, grapefruit juice, and similar citrus fruits while taking certain medications can cause a higher concentration of those drugs in your system. This may lead to unwanted side effects, or even an overdose.
There are more than 85 drugs that are known to interact with grapefruit, pomelos, tangelos, and Seville oranges. The chemicals in these fruits are known to inhibit CYP34A, just as CBD does. For this reason, if you shouldn’t eat grapefruit while on a particular medicine, then you should also avoid CBD.
There are broad categories of drugs that are known to interact with grapefruit — and may also interact with CBD, including:
- blood thinners
- medications that treat cancer
- antiepileptic drugs (AEDs)
- blood pressure medications
- medications to lower cholesterol
- erectile dysfunction medicines
- prostate medications
- GI medications, such as to treat GERD or nausea
- heart rhythm medications
- mood medications, such as to treat anxiety, depression, or mood disorders
- pain medications
If your medication falls into one of these classes, check the label or packaging for a grapefruit warning. Some specific medicines within these groups may not have a known negative interaction with grapefruit. If you have any questions, consult with your doctor.
Should I Take CBD?
CBD is considered to be safe, with few side effects. However, you should talk to your doctor first if you are considering trying CBD to alleviate symptoms of a condition or experience the overall general wellness benefits.
Your healthcare provider can help you determine if it is safe to take CBD in conjunction with your current medications. They may even order blood work to make sure that you are getting the proper levels of medication while taking CBD. Depending on their experience with CBD, your physician may also be able to suggest a particular product, serving size, or schedule for taking CBD.
If you are currently taking prescription or over-the-counter medications for any medical or mental health condition, do not stop taking them in order to try CBD. Consult with your doctor about using CBD, how it may interact with your medications, and only stop these medicines if your doctor says that it is safe to do so.
You may also ask your doctor about using topical CBD products, which typically do not enter the bloodstream. A CBD lotion, cream, or salve applied to an affected area may be a way to take advantage of the benefits of CBD without it affecting how your body processes your other medicines. Keep in mind that topical products that are designed to be transdermal, like some CBD patches, may still cause an interaction.
How to Buy CBD from a Trusted Source
If you have talked to your doctor about using CBD, and are confident that it will not negatively affect the medications that you take, you may be ready to take the next step. But with so many CBD products on the market, it can be hard to know where to start. We are here to help.
At Green Wellness Life, we only offer independently tested CBD products made from hemp grown in the United States. You can trust the quality of the CBD that we sell — and verify it yourself by reviewing test results. To learn more about CBD or for assistance with selecting a product that is right for you, reach out today at 888-772-7875, or email us at any time.
Tried & True CBD Products To Consider
While we are always here to help you select the right CBD product for you, we also wanted to include some of our favorite products for your consideration. If you’re new to CBD the sheer number of brands and types of products available can be overwhelming. We’ve selected a few favorites based on our own experiences and the experiences and feedback provided by our customers.
Papa & Barkley Releaf CBD Drops
Papa & Barkley’s Releaf CBD Drops combine the benefits of full spectrum CBD with a delicious lemongrass ginger flavor. The tincture is easy to take, which makes it great to work into a daily routine. The drops are also produced using a whole plant infusion process, which allows your body to metabolize the cannabinoids faster.
WYLD CBD Gummies
WYLD CBD Gummies are delicious edibles designed for snackers. The gummies contain broad spectrum CBD combined with real fruit. There are no artificial flavors or coloring and the gummies come in two different flavors: lemon and raspberry. We’ve tried a lot of gummies and we feel WYLD gummies are hands down some of the best tasting CBD gummies available.
Endoca Hemp CBD Whipped Body Butter
Endoca’s whipped body butter adds a smooth, moisturizing texture to your skin. It’s great for targeted pain relief, workout recovery, burn relief, and relief from skin irritation or inflammation. The body butter may be able to help with acne, eczema, psoriasis, and a number of other skin-related conditions.
Social CBD Transdermal Patch
Social’s CBD Patch is a transdermal patch, which means it does get absorbed into the body. The patch is high-strength and comes in 20 and 60mg CBD options. CBD from the patch is released over 12 to 24 hours, which allows you to earn the calm and relaxing effects of CBD over a decent duration of time. It can provide targeted relief in the general area where it is applied.
For more product recommendations or to learn more about CBD and what it can do for you, do not hesitate to call 888-772-7875, press the live chat button, or fill out a contact form to speak with one of our CBD product experts.
About David Kranker
David Kranker is the digital marketing manager at Green Wellness Life. David is passionate about CBD and making well-sourced CBD information/research accessible to all. David likes to keep his finger on the pulse of the CBD industry to report the latest studies, statistics, and findings from the community.