The Grapefruit Effect: CBD and Drug Interactions

CBD (cannabidiol), which comprises as much as 40% of cannabis plant extract, is an amazing chemical compound. It provides strong anti-inflammatory, analgesic, anti-epileptic, and anti-anxiety properties, without the intoxicating effects caused by THC (tetrahydrocannabinol).

Many hemp-based CBD oil companies emphasize the safety of using CBD for just about any condition. Unfortunately, they often ignore the fact that CBD can interact with other drugs in significant ways. These interactions can be problematic in many cases, and deadly in others, increasing the effects of the companion drug in ways that can greatly change the appropriate dose.

How Does CBD Affect Other Medications?

CBD inhibits the ability of a group of liver enzymes called cytochrome P450 (CYP) to metabolize medications. Our bodies use these enzymes to metabolize more than 60% of the medications currently on the market. The extent to which this happens depends on the amount of CBD used, the unique metabolism and genotype of the consumer, and whether isolated CBD or a whole-plant extraction is used.

These effects are more likely to occur when CBD products are eaten. When eaten, CBD passes through the liver and interacts with the CYP enzymes before it hits the blood stream and affects the body. This is different from smoking, vaping, topical, or sublingual administration, where CBD hits the blood stream and affects the body before it goes to the liver. It’s important to note, however, that even with direct-to-bloodstream administration methods, some CBD eventually reaches the liver and interacts with the CYP enzymes, potentially creating the inhibitory effects.

Research is sparse about just how much CBD is needed to inhibit the effects of other medications. One small-group clinical trial using 40 mg of a whole-plant, CBD-rich sublingual spray found no interactions with CYP enzymes. Another clinical trial with the same product found that 25mg of orally administered CBD significantly blocked the metabolism of an anti-epileptic drug. Perhaps the different results were caused by the different administration methods (sublingual vs oral), but more research is needed to find out for sure.

Why is this Relevant?

When drugs are prevented from being metabolized, it can cause many unwanted effects. For example, doctors rely on the effects of liver metabolization when determining the dosing of chemotherapy drugs. Since CBD inhibits metabolization, cancer patients who use CBD in conjunction with chemotherapy can end up with higher concentrations of the cancer-destroying chemicals in their blood. Since the goal of chemotherapy is to use the highest dose possible without killing the patient, this higher blood concentration is potentially catastrophic.

As another example, CBD inhibits metabolizatioon and therefor increases the blood concentration of many popular anti-seizure medications. Epileptics using CBD in combination with these medications must have their blood levels carefully monitored or risk overdose.

Because of these and other interactions, patients who use pharmaceutical treatment methods (prescription or over-the-counter) must fully disclose their CBD self-medication plans to their doctors to avoid unwanted, and possibly deadly, effects.

Interestingly, this inhibitory effect is key in understanding how CBD reduces the psychoactive effects of THC. When ingested without CBD, THC metabolizes into hydroxy-THC, a much more potent metabolite of THC. When consumers are pre- or co-treated with CBD, the conversion is slowed down, causing THC, which is less potent than the hydroxy-THC, to remain in the blood stream for longer. This extends the duration, but lessening the strength of the psychoactive effects.

How do I know if my Medications Are Affected by CBD?

It’s difficult to find studies on specific interactions between CBD and other drugs. Research is limited. Luckily, there’s a back door to the information you need.

You may have heard that with some medications, patients are cautioned against eating grapefruit. That’s because grapefruit contains several compounds that inhibit CYP enzymes. We now know that CBD inhibits CYP enzymes even more than grapefruit!

Therefore, if you are cautioned to avoid eating grapefruit when taking a specific medication, you should definitely avoid taking CBD with that medication as well. And ALWAYS talk to your doctor about your CBD use if you are taking (or are considering) any other medications. The consequences could be a matter of life or death!


Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. 1998. Br J Clin Pharmacol. 2004.

Devitt-Lee, A. CBD-drug interactions: role of cytochrome P450. 2015.

Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015.

Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci. 2011.

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