This is not a theoretical risk
Cannabinoids are metabolised by, and inhibit, several of the same liver enzymes that process common prescription drugs. The clearest documentation comes from the Epidiolex prescribing information, since that is a regulated medicine with a required interaction section.
This page is general information. Take your specific medication list to a pharmacist.
What CBD does to liver enzymes
Per the current Epidiolex label, CBD inhibits CYP2C19 (moderate), CYP2C8, UGT1A9, and CYP1A2 (weak), and either induces or inhibits CYP2B6. CBD itself is metabolised by CYP3A4 and CYP2C19.
- • CYP1A2 substrates: theophylline, tizanidine
- • CYP2C19 substrates: clopidogrel
- • P-glycoprotein substrates: everolimus, sirolimus, tacrolimus, digoxin
- • UGT1A9 substrates: mycophenolate mofetil
Warfarin
THC inhibits CYP2C9-mediated metabolism of warfarin. A 2019 review in Basic & Clinical Pharmacology & Toxicology documented an index case of a 27-year-old man on warfarin for a mechanical valve presenting with an INR of 4.6 after recreational cannabis use, plus a literature case with INR above 10 and bleeding, and a patient on CBD who required a 30% warfarin dose reduction.
If you take warfarin and use cannabis, your INR monitoring needs to know about it.
Clobazam and valproate
Coadministration of CBD with clobazam produces roughly a threefold increase in plasma concentrations of N-desmethylclobazam, clobazam's active metabolite, via CYP2C19 inhibition. Increased sedation follows.
CBD with valproate increases the incidence of liver enzyme elevations. The Epidiolex label carries a hepatocellular injury warning with required baseline and periodic liver function testing.
Immunosuppressants
Tacrolimus, sirolimus, and everolimus appear on the Epidiolex label as P-glycoprotein substrates. A published case report and a Phase I pharmacokinetic trial have examined the CBD–tacrolimus interaction specifically.
For transplant recipients this is not a margin-of-error situation. Involve your transplant team before using any cannabis product.
The general rule
If you take any prescription medication with a narrow therapeutic window — anticoagulants, antiepileptics, immunosuppressants, some cardiac drugs — treat cannabis as a drug that interacts, because it is one.