by Dr Linda Klumpers

Introduction to drug interaction

When products containing cannabidiol (CBD) are taken with other products, such as food or medicines, side effects can occur due to a drug-interaction. There are various types of drug-interactions that can take place, and in this article, we only focus on the type called metabolic interaction.

Most compounds, including CBD, are broken down, or metabolized by enzymes. This mostly takes place in the liver. These enzymes can be stimulated (induced) or blocked (inhibited) by medication, herbs, or foods. For example, a patient may be taking CBD and drug A. In the case of enzyme inhibition, if CBD and drug A are both competing for the enzyme, one will bind to the enzyme first – let’s say CBD. The enzyme will then predominantly metabolize CBD before drug A gets a chance to be metabolized. In this example, even if the patient only took one pill of drug A, the patient could experience the effects of two pills of drug A due to the slowed down metabolic interaction with CBD. Figure 1 demonstrates this concept.

How CBD-drug interaction works

The enzyme called CYP3A4 is widely expressed in the liver and gut and is generally considered to be the most important drug-metabolizing enzyme. CBD is able to inhibit CYP3A4 as well as other enzymes, such as CYP2C19, and can compromise the breakdown of many drugs. (Stout et al., 2015) It also works the other way around, as some medicines are able to inhibit CYP3A4 and affect the metabolic processing rate of CBD. The latter has not been structurally researched in studies. Drugs, herbs, and foods can all have drug-interactions. Grapefruit for example inhibits CYP3A4 and thus is able to slow medicine metabolism. (Uno et al., 2006)

Make sure to remember that a slower drug-metabolism leads to higher drug concentrations, which could be harmful and potentiate unwanted adverse effects. Similarly, high metabolic activity will lower the drug concentration and the drug would not provide sufficient health benefits. Be careful when taking, starting, or stopping medications and supplements. Your doctor can determine the right CBD product, prescribe alternative medications, or monitor blood level values of important medications.

Some examples of drug interaction with CBD

Studies are ongoing to demonstrate the interactions between CBD and medications. One study revealed that in children taking clobazam and CBD (both being used for refractory epilepsy), levels of the active metabolite of clobazam was significantly increased, implying that blood levels need to be monitored. (Geffrey et al., 2015) This effect was likely through enzyme inhibition by CBD. Similarly, in patients treated with CBD, blood levels of anti-epileptic drugs like topiramate and rufinamide increased, and even reached levels that were higher than the therapeutic range. (Gaston et al., 2017)

Highlights

• CBD can interact in the body with medicines, herbs, and food
• CBD can increase the blood concentration of certain concomitant medications, such as anticonvulsant clobazam
• CYP3A4 and CYP2C19 are the most important enzymes for CBD metabolism
• If your medication has a “Grapefruit Warning” it is likely you should avoid taking CBD in conjunction with it
• It’s important to consult your healthcare provider when taking CBD with other medications