CYP450: the enzyme family that breaks down CBD

Ten notes on one enzyme family

1. A label counts milligrams. What the body does with them afterwards is enzyme chemistry, and that is written up in a different kind of literature entirely.
2. A major share of that chemical work in the human body belongs to a single enzyme family: cytochrome P450.
3. CYP is the short form of the cytochrome P450 superfamily. One abbreviation, many separate enzymes, each with its own designation.
4. The numbers and the letter work like an address. CYP3A4 means family 3, subfamily A, isoform 4.
5. CYP2C19 is read the same way: family 2, subfamily C, isoform 19. Different family, different subfamily, different isoform.
6. Pharmacokinetic reviews describe this family as the principal oxidative route for a large proportion of commonly used medicines [1].
7. Human liver microsomes are subcellular fragments of liver tissue in which the P450 enzymes stay functional. Useful for measuring enzyme activity. Not a person, and not a whole liver either.
8. Jiang and colleagues used that preparation in 2011 to identify the cytochrome P450 enzymes responsible for metabolising cannabidiol. CYP3A4 and CYP2C19 were the main contributors to the conversions measured, with further isoforms involved to a lesser extent [2].
9. The 2018 systematic review by Millar and colleagues found the human data on cannabidiol pharmacokinetics uneven across administration routes and formats, with substantial gaps in the published record [1].
10. Two substances travelling the same enzymatic route is described in that review as the general basis for a pharmacokinetic interaction [1]. A general basis is not a measured number for one specific combination.

Cytochrome P450, read closely

Family, subfamily, isoform

CYP is not one enzyme. It is a superfamily, cytochrome P450, made up of related proteins that each carry their own designation. The designation is built in three steps. The number straight after CYP gives the family. The letter gives the subfamily. The final number picks out the individual isoform. So CYP3A4 sits in family 3, subfamily A, and is isoform 4. CYP2C19 sits in family 2, subfamily C, and is isoform 19. Two names, two addresses, two different proteins. Once the code is readable, a sentence lifted from a study stops looking like alphabet soup and starts being specific. That matters here, because the cannabidiol work names particular isoforms rather than the family as a block.

Why the name keeps turning up

Scale is the answer. Pharmacokinetic reviews describe the cytochrome P450 family as the principal oxidative route for a large proportion of commonly used medicines [1]. Take that sentence apart. An oxidative route is the chemical step that alters a molecule once it is inside the body. Principal means most of the traffic goes that way. A large proportion of commonly used medicines means this is not a curiosity reserved for rare compounds, it is the ordinary road. Cannabidiol shows up in the same literature for the same reason. Researchers asked which of these enzymes handle it, and the 2011 identification work answered that question for one laboratory preparation [2].

A 2011 test on liver tissue

Start with the material, because the material sets the limits of what can be concluded. Human liver microsomes are subcellular fragments of liver tissue, prepared so the P450 enzymes inside them keep working. What you get is measurable enzyme activity, isolated from everything else a living body is doing at the same moment. Jiang and colleagues used that preparation in 2011 with one stated aim: identify the cytochrome P450 enzymes responsible for the metabolism of cannabidiol [2]. Among the conversions they measured, CYP3A4 and CYP2C19 came out as the main contributors, and further isoforms took part to a lesser extent [2]. So the route is mapped. The pace at which anything moves through a living person is a separate question, and this design was never built to answer it.

• The material was human liver tissue prepared as microsomes, not a volunteer and not a whole organ [2].
• The question was narrow and chemical: which cytochrome P450 enzymes act on cannabidiol [2].
• Most of the measured activity sat with two isoforms, CYP3A4 and CYP2C19 [2].
• Other isoforms appeared in the results as well, with smaller contributions [2].
• The names of the enzymes are on record. Quantities for a given person, format and amount are not part of this design.
• An identification study stands where it stands. It tells you which door the molecule goes through, not how wide that door is on any particular day.

The human record, as of 2018

A systematic review is a structured sweep of what has already been published, worked to a set method rather than by preference. Millar and colleagues ran one in 2018 on the pharmacokinetics of cannabidiol in humans, and the picture they reported is patchy. Human data sits unevenly across administration routes and across formats, and the published record carries substantial gaps [1]. That finding is worth more than it first looks. It tells you which sentences about cannabidiol in the body rest on human measurement, and which ones are being carried by inference. The same review also sets out the shared-route idea: when two substances are handled by the same enzymatic pathway, that shared route is the general basis for a pharmacokinetic interaction between them [1]. A general basis, stated as a principle. Not a value for any one pairing.

• The review looked at human data, which is a stricter category than laboratory data [1].
• Coverage differs by administration route, so a figure from one route does not transfer to another [1].
• Coverage also differs by format, and the gaps in the record are described as substantial [1].
• Sharing an enzymatic route is presented as the general basis for interaction between substances [1].
• What a review of this kind does not produce is a number for cannabidiol alongside one named medicine.
• Where the evidence is thin, the honest sentence is that the measurement has not been made.

What sits on your side of the bottle

There is a version of this topic that belongs to laboratories, and a version that fits on a kitchen table. On your side there is a bottle, a label, and possibly a repeat prescription. The enzyme names cannot tell you how those three sit together, and neither can a web page. Someone holding your full medicine list can look at it properly, which is why a pharmacist or a doctor is the right person to ask, particularly with an existing prescription. What we can do is make the bottle itself readable. Every Cibdol batch is analysed independently and the report is published, so the milligrams printed on the label are checkable before anything joins a routine. Working with cannabinoids since 2014 has taught us which details people actually want in writing, and which ones are still open.

• Write down every prescription and over-the-counter product you take, by name, including the occasional ones.
• Note the format you use, oil or capsule or something else, since the published human data differs by route [1].
• Copy the milligrams per serving straight from the label.
• Bring the batch analysis for your bottle, which we publish for every batch.
• Keep the question specific, because a specific question is the one that can be answered from records.
• Two enzyme names are documented for cannabidiol, CYP3A4 and CYP2C19 [2]. The rest is a conversation, not a page.