Cannabidiol as a cytochrome P450 inhibitor: a narrative review of laboratory inhibition constants and human interaction studies

Description

Cannabidiol is a prescription medicine for rare, severe childhood epilepsies, and the children who take it are almost never on it alone. It is added to clobazam, to valproate, to whatever else is already being given. Most of those drugs are cleared by the cytochrome P450 enzymes in the liver, and cannabidiol slows some of those enzymes down. The other drug then builds up, and the sedation that follows is a dosing problem rather than a mystery, provided somebody knows which pairs to watch. Which enzymes, and by how much, is unsettled. Experiments on human liver preparations do report inhibition, but the concentration needed varies by a wide margin from one report to the next. Part of that is chemistry: cannabidiol is greasy, it sticks to plastic and to protein, and how much of it is loose in the test system often goes unmeasured. The studies in people are small, and each looks at one or two drug pairs. This project sets the laboratory numbers beside the human ones and asks whether they agree. Most of the work is arithmetic, done carefully, on papers other people have already written.

Student responsibilities

Read up on how the liver clears drugs and how enzyme inhibition is measured. Take one part of the evidence, read the papers for it, build the table that goes with it, and write that section of the review.