CBD and medication: the grapefruit effect in numbers

Enzymes clear most medicines, chiefly in the liver and the gut wall. The best known belong to the cytochrome P450 family, written CYP. If a substance slows one of them, the medicine that enzyme should break down accumulates, and its effect and side effects may grow.

CYP3A4 carries a large share of the load: according to Medsafe, New Zealand's medicines agency, it handles more than 50% of medicines. A 2023 review in Frontiers in Psychiatry lists CYP2C9, CYP2C19, CYP2D6 and CYP3A as enzymes CBD slows, with a possible effect on CYP1A2, CYP2B6 and CYP2C8. Two conjugation enzymes, UGT1A9 and UGT2B7, may be slowed as well. A good part of these results comes from laboratory tests on cells or isolated enzymes.

The role of these enzymes, and liver monitoring under Epidyolex, are explained in our article on CBD and the liver. You will find CBD's interactions with medicines and supplements, graded by strength of evidence and by severity and listed with their sources, in our interactions dossier.

Grapefruit is the standard example since its effect is well documented. A 2013 review in the CMAJ counted over 85 medicines that interact with the fruit or are expected to, 43 of them with possibly serious consequences.

Its mechanism is precise. Furanocoumarins, compounds found in the fruit, irreversibly inactivate CYP3A4 in the small intestine, and one whole grapefruit or 200 ml of juice is enough. The effect peaks when the fruit is eaten in the 4 hours before the medicine, and about 25% of it persists after 24 hours. Medicines given intravenously bypass the gut and are not affected.

The comparison works for the principle: a harmless-looking substance alters the real dose of a medicine. It breaks down on the enzymes involved and on the amounts.

The most solid data come from the approval file of Epidyolex, the only medicine based on CBD. The European Medicines Agency publishes its summary of product characteristics, which describes studies in healthy volunteers. They received 7.5 to 12.5 mg of CBD per kilo twice a day, about 1,000 to 1,750 mg a day for 70 kg.

Four findings stand out:

• With clobazam, an antiepileptic, the active metabolite N-desmethylclobazam reaches 3 to 4 times its usual level, probably because CYP2C19 is inhibited. Drowsiness affected 43% of patients on CBD and clobazam, compared with 14% on CBD without clobazam.
• Exposure to everolimus, an immunosuppressant, rises about 2.5 fold. The agency puts this down to a gut transporter, P-gp, and names tacrolimus, sirolimus and digoxin as open to the same risk.
• Total caffeine exposure increases by 95%, which makes CBD a weak inhibitor of CYP1A2.
• Midazolam, the medicine used as a marker of CYP3A4, showed no change in exposure. At these doses, CBD does not act on this enzyme the way grapefruit does.

According to the same document, liver enzymes rise more often when CBD is combined with valproate. A case published in 2017 concerns a 44-year-old patient followed for epilepsy who also took warfarin, an anticoagulant. When CBD reached 10 mg per kilo per day, his INR, the clotting marker monitored under this treatment, went from 2.22 to 6.86. His warfarin dose had to be reduced by about 30%.

Every one of these measurements involves medicinal doses. Epidyolex is prescribed at 5 to 20 mg per kilo per day, up to 25 mg in one indication, which is 350 to 1,400 mg a day for 70 kg. The 2023 review judges strong interactions likely with high oral doses of CBD, around 700 mg. It also reports a rise in citalopram, an antidepressant, with CBD products at 200 to 800 mg a day.

For the doses in products sold to the public, there are no studies. A lack of data is no proof of safety, and the agencies say so plainly. EFSA set on 9 February 2026 a provisional level of 2 mg a day for a 70 kg adult, without being able to establish safety for people taking medicines. The UK Food Standards Agency advises people on medication not to take CBD. These benchmarks are compared in our article on how much CBD per day.

Swallowing CBD is also a legal issue in France, where CBD foods and supplements must be withdrawn from sale, as explained in our overview of CBD regulation in 2026.

Ask the pharmacist or doctor who knows your treatment. They can check each molecule one by one, which no general list can do. Before that conversation:

1. Write down all your medicines, over-the-counter ones included, along with supplements and St John's wort, which also acts on these enzymes.
2. Mark those with a narrow margin, where a small change in concentration has consequences: anticoagulants such as warfarin, immunosuppressants such as tacrolimus or everolimus, antiepileptics, digoxin.
3. Do not adjust the dose of a prescribed medicine yourself, whether to "make room" for CBD or the other way round.
4. Tell the medical team about CBD before surgery, as you would for any product you use. The question is reviewed in our article on CBD before anaesthesia.
5. Plan for drowsiness: the Epidyolex summary states that alcohol and other nervous system depressants can increase it.

For the side effects of CBD itself, see our article on its side effects. Older people often take several medicines, and their situation is covered in our article on CBD for seniors.