CYP450

Cytochrome P450 (CYP450) is a superfamily of hepatic enzymes responsible for metabolising approximately 75% of prescription medicines. Different isoforms handle different drug classes — clinical decisions about cannabinoid co-prescribing depend on understanding which isoforms matter for which patient.

**Most relevant isoforms in cannabinoid prescribing:** - **CYP3A4** — the most abundant hepatic isoform; metabolises tacrolimus, cyclosporine, statins, many antidepressants, azole antifungals, calcium-channel blockers. Both THC and CBD inhibit CYP3A4 to clinically relevant degrees at higher doses. - **CYP2C9** — metabolises warfarin, phenytoin, losartan, NSAIDs. Cannabinoid inhibition can substantially raise warfarin levels and bleeding risk. - **CYP2C19** — metabolises clobazam (an active metabolite N-desmethylclobazam levels rise with CBD), some antidepressants, proton-pump inhibitors. - **CYP2D6** — metabolises some antidepressants and beta-blockers; less consistently affected by cannabinoids.

**Clinical strategy** — comprehensive medication review at every cannabinoid initiation, monitoring (warfarin INR, clobazam levels in seizure patients, LFTs), and dose-staging where interactions are predictable. Many CYP-substrate medications can be safely co-prescribed with cannabinoids; others mandate alternatives. The doctor will not initiate cannabinoid therapy without working through this list.