CBD and other commonly used medicines: what is known for each?

Medicines and the importance of their interactions

From peer-reviewed publications and drug labels: the warnings, most important first. The same warnings also appear in the interaction checker. A medicine that is not listed can still interact with CBD.

How does the interaction happen?

It helps to split the medicines on this page into two groups. The first group is medicines that change the level of CBD. CBD is broken down in the liver mainly by the CYP3A4 and CYP2C19 enzymes; rifampin and St. John's wort, which speed up these enzymes, lower the CBD level, while ketoconazole, which slows CYP3A4, increased the CBD level about 2 times in a study with the approved mouth spray containing THC and CBD. In the study with the approved CBD medicine taken by mouth, however, the effect of itraconazole, a strong CYP3A4 inhibitor, was small (the CBD level rose by less than 10%). The CBD level was also found to be higher in children taking levothyroxine. (EMA Epidyolex prescribing information 4.5 and 5.2, FDA Epidiolex label §7.1 and §12.3 (05/2026), PMID 23750331, PMID 37631333)

The second group is medicines whose level CBD changes. CBD slows the CYP1A2 enzyme weakly and CYP2C19 moderately. That is why the blood levels of theophylline and tizanidine, which are broken down by CYP1A2, and of omeprazole, which is broken down by CYP2C19, can rise with CBD. Based on laboratory data, the prescribing information for approved CBD says that CBD may also slow the CYP2C8 enzyme, and recommends considering a lower dose of a medicine broken down by this enzyme if side effects appear; the prescribing information does not include a human study with this enzyme. The diabetes medicine repaglinide is broken down by CYP2C8 and CYP3A4; the prescribing information for repaglinide says that with medicines that slow these enzymes, a dose reduction and more frequent blood sugar checks may be needed. No human study looking at repaglinide together with CBD was found. (FDA Epidiolex label §7.2 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, PMID 37313955, Repaglinide prescribing information §7 and §12.3)

There is also an issue that does not depend on drug levels: the liver. CBD can raise liver enzymes. The prescribing information states that there is not enough data to judge the risk together with other medicines that can affect the liver, and that liver monitoring should be restarted when such a medicine is added or its dose is changed. (FDA Epidiolex label §5.1 and §7.3 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5)

There is no documented interaction with the birth control pill or diabetes medicines. The medicines known to make the birth control pill less effective are usually medicines that speed up enzymes (e.g. rifampin, St. John's wort); in a drug-level study, approved CBD did not speed up CYP3A4. The prescribing information for the approved mouth spray containing THC and CBD, however, notes that this medicine speeds up drug-metabolizing enzymes and transporters in the laboratory, and recommends an additional barrier method for women using hormonal birth control. Still, no study has looked at the birth control pill together with CBD. (Birth control pill prescribing information §7.1, EMA Epidyolex prescribing information 5.2, THC and CBD oromucosal spray (Sativex) prescribing information 4.5)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

1. Drug-level study

   Rifampin: CBD level fell by about a third

   In a drug-level study with approved CBD, rifampin (600 mg a day), a strong enzyme inducer (speeder), lowered the blood level of CBD by about 32% and the level of its active breakdown product 7-OH-CBD by about 63%. In a study with the THC/CBD mouth spray, the CBD level also fell by half or more. How much this drop reduces the effect of CBD is not known.

   Source: FDA Epidiolex label §7.1 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, PMID 23750331

2. Official drug information

   St. John's wort: may lower the CBD level

   The European product information lists St. John's wort together with strong enzyme inducers such as carbamazepine and enzalutamide, and says they may lower the CBD level to an extent similar to rifampin. No study looking directly at St. John's wort and CBD was found; the enzyme-inducing strength of St. John's wort products can also vary greatly from product to product.

   Source: EMA Epidyolex prescribing information 4.5, Birth control pill prescribing information §7.1

3. Drug-level study

   Ketoconazole: CBD rose about 2 times with the spray (2013)

   In a study in healthy men, the antifungal ketoconazole increased the blood level of CBD about 2 times after the THC/CBD mouth spray. In the study with approved CBD taken by mouth, however, itraconazole, a strong CYP3A4 inhibitor, raised the CBD level by less than 10%, and fluconazole by about 22%; the US prescribing information does not consider the effect of fluconazole clinically significant. The result may vary with the product and the amount of CBD.

   Source: PMID 23750331, FDA Epidiolex label §12.3 (05/2026), PMID 38794183

4. Drug-level study

   Omeprazole (PPI): level rose about 3 times (2023)

   In 18 healthy volunteers, a single dose of a CBD-dominant cannabis extract (640 mg CBD and 20 mg THC) increased the total amount in the blood of omeprazole, which is broken down by CYP2C19, about 3 times. The European product information also states that CBD may raise the level of medicines broken down by CYP2C19, such as omeprazole. The clinical importance of this was not reported, and the other stomach protectors have not been studied with CBD. In the opposite direction, omeprazole did not clearly change the CBD level in a study with the THC/CBD spray.

   Source: PMID 37313955, EMA Epidyolex prescribing information 4.5, PMID 23750331

5. Drug-level study

   Theophylline and tizanidine: CBD slowed the CYP1A2 pathway (2021)

   In healthy volunteers taking approved CBD (750 mg twice a day), the total amount in the blood of caffeine, which is broken down by CYP1A2, rose about 2 times (95%); this shows that CBD weakly slows this enzyme. The prescribing information says that the levels of theophylline and tizanidine, which are broken down the same way, may also rise; for medicines where even a small increase can cause serious side effects, it recommends that the doctor consider a dose reduction. In this study, 6 of 16 people left the study because of raised liver enzymes.

   Source: PMID 33951339, FDA Epidiolex label §7.2 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5

6. Official drug information

   Tizanidine's label: asks to avoid weak CYP1A2 inhibitors

   The prescribing information for tizanidine recommends avoiding use together with medicines that inhibit CYP1A2 moderately or weakly; if they must be used together and low blood pressure, a slowed heart rate or excessive drowsiness occurs, it recommends that the doctor lower the tizanidine dose or stop the medicine. Tizanidine also increases drowsiness together with other substances that cause sleepiness. CBD is not named in this list; however, the prescribing information for approved CBD describes CBD as a weak CYP1A2 inhibitor, and CBD can also cause drowsiness.

   Source: Tizanidine prescribing information §7.2 and §7.4, FDA Epidiolex label §5.2 and §7.2 (05/2026)

7. Observational study

   Levothyroxine: CBD level was about 2 times higher in children (2023)

   In a study of 22 children with drug-resistant epilepsy who were using CBD, the CBD level measured in the morning was higher in the 7 children who were also taking levothyroxine (median 100.7 ng/mL; 37.3 ng/mL in those not taking levothyroxine); the calculated increase was about 110%. The same team had also recorded this interaction in an earlier small study. The reason is not known; the authors think thyroid hormones may affect the enzymes that break down CBD. In the opposite direction, in 201 healthy adults, 4 weeks of CBD did not change thyroid tests (TSH and thyroid hormones) compared with placebo; this was not studied separately in people taking levothyroxine.

   Source: PMID 37631333, PMID 33280111, PMID 40622698

8. Official drug information

   Medicines that affect the liver: not enough data

   The prescribing information for approved CBD says that CBD can raise liver enzymes in a dose-related way, that this rise is more common together with valproate, and that there is not enough data to judge the risk together with other medicines that can affect the liver. In healthy volunteers, too, liver enzymes rose above 3 times the upper limit of normal in 5.6% of those taking 5 mg/kg of CBD a day for 4 weeks.

   Source: FDA Epidiolex label §5.1 and §7.3 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5, PMID 40622698

9. Controlled study

   Diabetes medicines: CBD did not improve blood sugar (2016, 2026)

   In a controlled study in which 62 patients with type 2 diabetes not using insulin were split into five groups, 100 mg of CBD twice a day for 13 weeks did not significantly improve blood sugar results compared with placebo. In a small controlled study of 16 overweight adults without diabetes, 4 weeks of low-dose CBD (30 mg every 12 hours) also did not affect a glucose tolerance test compared with placebo. Approved CBD did not change the blood level of tolbutamide, a diabetes medicine. There is no documented interaction with diabetes medicines; CBD does not replace these medicines.

   Source: PMID 27573936, PMID 41167732, FDA Epidiolex label §12.3 (05/2026), MeSH Tolbutamide

10. Official drug information

    Birth control pill: no human data

    No published human study looking at the birth control pill together with CBD was found. The prescribing information for the pill says that enzyme inducers such as rifampin and St. John's wort can make the pill less effective and that an additional or different method of protection is then needed; in a drug-level study, approved CBD did not speed up CYP3A4. The prescribing information for the approved mouth spray containing THC and CBD, however, gives a warning: because this medicine speeds up drug-metabolizing enzymes and transporters in the laboratory, it may make hormonal birth control less effective. The prescribing information states that this is not known for certain and, as a precaution, recommends an additional barrier method (such as a condom) for women using a hormonal method during treatment and for three months after stopping. The US and European prescribing information for the approved CBD medicine has no such warning. A lack of data does not mean it is safe.

    Source: Birth control pill prescribing information §7.1, EMA Epidyolex prescribing information 4.5 and 5.2, FDA Epidiolex label §7 (05/2026), THC and CBD oromucosal spray (Sativex) prescribing information 4.4 and 4.5

What is monitored?

• Theophylline: if you have nausea, vomiting, a headache that does not go away, trouble sleeping or palpitations, tell your doctor; your doctor may measure your theophylline blood level. (Theophylline prescribing information, FDA Epidiolex label §7.2 (05/2026))
• Tizanidine: if you have dizziness, low blood pressure, a slowed heart rate or excessive drowsiness, tell your doctor right away. (Tizanidine prescribing information §5.1 and §7.2)
• Liver: if you take a medicine that can affect the liver, talk with your doctor about liver tests before starting CBD and during the first months. If you notice unexplained nausea, vomiting, pain in the upper right part of your belly, fatigue, loss of appetite, yellowing of the skin or the whites of the eyes, or dark urine, tell your doctor right away. (FDA Epidiolex label §5.1 (05/2026), EMA Epidyolex prescribing information 4.4) CBD and valproate
• Rifampin or St. John's wort: if you use CBD as a treatment (e.g. approved CBD for epilepsy), your doctor will assess whether the effect of CBD changes when you start or stop these products. (FDA Epidiolex label §7.1 (05/2026), EMA Epidyolex prescribing information 4.5)
• Diabetes: keep checking your blood sugar as usual; do not replace your diabetes medicines with CBD. (PMID 27573936, PMID 41167732, NIH NCCIH)

Frequently asked questions

References

Last reviewed: October 27, 2026. On this date, each source was opened and checked against the related sentence.