Most people are aware of the potential risk that comes when combining medications without prior approval from a doctor, but many don’t know that there is also a risk of complications when taking certain natural supplements. Even some types of food can trigger a harmful reaction when combined with certain medications. What causes these complications, though? And is there any way to avoid it?


Surprisingly there are a lot of medications that include a warning not to combine them with grapefruit or grapefruit juice. But why grapefruit? What does a grapefruit contain that creates such a dangerous combination with prescription drugs? 

Grapefruit and grapefruit juice are both great additions to a healthy diet under normal circumstances. It contains important servings of vitamin C and potassium, which are essential to a healthy lifestyle. However, grapefruit also disrupts the absorption process when combined with certain medications, allowing either too much or too little medication to enter the blood. This can be dangerous for a number of reasons, from increased risk of liver damage to a potentially life threatening situation occurring because the medication isn’t reaching its intended target. 

There are a number of medications that should not be combined with grapefruit juice, some examples include: 

  • Statin drugs to lower cholesterol, like Zocor and Lipitor
  • Drugs that treat high blood pressure, such as Procardia and Adalat CC
  • Organ-transplant rejection drugs, including Sandimmune and Neoral
  • Anti-anxiety drugs like buspirone
  • Corticosteroids used for treating Crohn’s disease or ulcerative colitis, like Entocort EC and Uceris
  • Drugs that treat abnormal heart rhythms, such as Pacerone and Nexterone
  • Antihistamines like Allegra

It is important to keep in mind that grapefruit does not affect all drugs in the above categories and that the above list is not inclusive. Patients should always check with their doctor. Also notable is the severity of the interaction will vary in each person and depends on the drug and the amount of grapefruit consumed, as well as an individual’s personal health and body chemistry. 

The question remains, though — why does grapefruit affect so many different types of medications? It really comes down to an enzyme called CYP3A4, which lives in the small intestine. Grapefruits contain compounds called bergamottin and 6’7’-dihydroxybergamottin that block the action of CYP3A4, keeping it from doing its job of metabolizing medications as they pass through the intestine [1]. In the next section, we’ll discuss what CYPs are and how they relate to cannabis products. 


Cytochromes (CYPs) are collectively a group of enzymes involved in the metabolization of drugs, accounting for almost 75% of the total metabolic process [2]. They oxidize steroids, fatty acids, and xenobiotics, and are important for hormone synthesis. In the human body there are six of these proteins that are involved in the metabolism of drugs. These proteins are CYP1A2, CYP2C9, CYP2D6, CYP3A4, and CYP3A5. The most important of these six, however, are CYP3A4 and CYP2D6. 

Normally, CYPs work to break down drugs in the system, leaving only the percentage that should be absorbed by the body. When the CYP process is disrupted, however, there is a risk of either increased or decreased activity by the enzymes which is where the complications begin. If the CYPs aren’t allowed to complete their metabolization as required, there is a risk of either too much or too little of a medication reaching the bloodstream. 

If a drug is not metabolized correctly it can accumulate within the body, possibly reaching toxic levels. This is obviously extremely dangerous and can result in an overdose. Along with grapefruit, there are a number of other substances that affect the process of CYPs in the body. These include St. John’s Wort, watercress, goldenseal, and cannabidiol (CBD). 


CBD is a competitive inhibitor to CYPs, but doesn’t appear to directly affect the absorption rate of medicines or the metabolization of them by CYPs. The problem comes from the fact that CBD binds itself to CYPs, thus preventing other medication from binding to CYPs, effectively slowing down CYPs ability to metabolize those medications [3]. This is a critical issue for prescription drugs which are usually prescribed in specific doses necessary for a certain patient’s needs. When that process is slowed or impeded, the dose required for the patient will be changed. 

For example, a single dose of CBD can block the CYPs from breaking down some medications. That means the medicine will stay active in the body for longer periods of time than intended or prescribed. Since medicinal treatment is fine tuned and specific for each person and condition, this is a problem and a potentially dangerous situation. 

In simple terms, CBD and CYP deactivate each other. 


Researchers have been investigating the effects of CBD on medication metabolization since the 1980s. The research suggests that CBD specifically interacts with cytochrome P450 by metabolizing the enzymes and inhibiting metabolization by the liver enzymes. When it occupies the site of enzymatic activity, the CBD will displace any other compounds competing with it, resulting in cytochrome P450 being unable to break down any other compounds. The amount of competition CBD presents depends on how tightly it binds to the active site of metabolization before and after oxidation. This factor depends on how much CBD was taken and of course the unique characteristics of the person taking the medication. It can also make a difference if the CBD is consumed as an isolate, with all other cannabinoid compounds removed, or a broad or full spectrum product, which leaves those other compounds intact. 

Studies have shown that a small enough dose of CBD will cause no noticeable effect on CYP activity, while still allowing it to retain its therapeutic properties. Unfortunately there is no clear cut-off for dosing to guarantee CBD won’t affect other medications since everyone’s biology is different and all medications are different chemically [4].  


It is important to understand that even the most natural and seemingly harmless supplements or foods otherwise considered healthy, may dramatically affect the medication a person takes. With this in mind, it is always important for patients to speak with their doctor when starting new medication or when considering a new therapy, even when that therapy contains all natural products. Human bodies are complicated and specialized, meaning that any little complication can set the entire thing on its side and lead to further issues. In order to avoid such issues, patients need to be proactive with their treatment options and make sure they are asking questions and being forthcoming about what their daily routine is. 

While it seems harmless on the surface, things like grapefruit, goldenseal, and CBD can drastically change the effectiveness of medications, especially prescription medications which are specially formulated at exact doses for specific purposes.