Short answer
CBD can change the blood level of some prescription drugs. It blocks two liver enzymes, CYP3A4 and CYP2C19. Those enzymes clear many medicines from the body. When CBD blocks them, a drug can build up to a level that causes side effects. Or a drug that needs those enzymes to become active can lose its effect. The FDA-approved CBD product Epidiolex carries a label warning about this. Human data is limited. Most evidence comes from epilepsy trials and lab tests on liver cells.
cannabis and opioid interactions
How CBD affects liver enzymes
Enzymes in the liver and gut wall break drugs into pieces the body can remove. CYP3A4 handles about half of all prescription drugs. CYP2C19 handles a smaller set. That set includes clopidogrel, some antidepressants, and proton pump inhibitors. CBD inhibits both enzymes. Lab work on human liver microsomes shows this. CBD also inhibits CYP2D6 and CYP2C9 at higher concentrations.
Grapefruit juice blocks CYP3A4 in the gut. CBD does the same thing, and it also acts in the liver. The Epidiolex label states that CBD is a CYP3A4 and CYP2C19 inhibitor.
Prodrugs lose activation
Some drugs are inactive until an enzyme converts them. Clopidogrel is one example. CYP2C19 makes the active form. If CBD blocks CYP2C19, the drug may work less.
Drugs with reported or likely interactions
These items come from the Epidiolex label, case reports, and clinical trials.
- Clobazam: CBD raises the level of its active metabolite, norclobazam. Trials found this at doses of 5 to 20 mg/kg per day.
- Valproate: The label notes a risk of liver enzyme rises when combined with CBD.
- Warfarin: CBD can raise INR. One case report described a rise in INR after a patient added CBD.
- Tacrolimus and cyclosporine: Both are CYP3A4 substrates. Levels can rise.
- Statins: Simvastatin and atorvastatin are CYP3A4 substrates.
- Benzodiazepines: Midazolam clearance drops in studies with CBD.
- Opioids: Fentanyl and methadone use CYP3A4.
- Antidepressants and antipsychotics: Many use CYP3A4 or CYP2D6.
- Heart rhythm drugs: Amiodarone and others.
Dose matters
Interaction strength tracks dose and blood level. Clinical trials used CBD from 200 mg to 1500 mg per day. The Epidiolex dose range is 5 to 20 mg/kg per day. A 70 kg adult at 20 mg/kg per day takes 1400 mg. Most over-the-counter CBD products sell 10 mg to 50 mg per dose. Low doses may carry less risk, but no study proves a safe cutoff. CBD has a half-life of 18 to 32 hours with repeat dosing. It can accumulate.
What to do
- Tell every prescriber and pharmacist that you use CBD. Give the dose and the product name.
- Ask if your drug has a narrow therapeutic index. Warfarin, tacrolimus, and levothyroxine are examples.
- Ask about a drug level test or an INR check after you start or stop CBD.
- Do not stop a prescription drug on your own.
- Avoid grapefruit juice while you take CBD. Both hit CYP3A4.
Unknown: no large human study has measured CBD interactions across all drug classes. The data is thin for most medicines.