CBD and CYP3A4: Why CBD May Affect Some Medications

WRITTEN by Edd

 | Last revised

Jul, 2022

Cannabidiol, or CBD, can provide relief from a wide range of symptoms, often with minimal side effects compared to many other medications used for the same purpose.

However, it does have some drawbacks. One of these is the way CBD can affect how your body responds to certain other medications. In particular, it interferes with the CYP3A4 enzyme.

The CYP3A4 enzyme is responsible for breaking down and metabolising cannabinoids in the body, as well as many prescription medications.

Having CBD in your system can slow the metabolisation of those drugs because the enzyme is already in use breaking down the CBD.

The reverse is also true. Medications that inhibit the CYP3A4 enzyme could slow the metabolisation of CBD.

But what does this mean, and how could it affect you?

CBD Oil And The CYP3A4 Enzyme

CYP3A4 (Cytochrome P450 3A4) is part of a group of enzymes that are responsible for oxidising chemicals and toxins within the body so they can be safely metabolised and removed from the body.

In fact, this enzyme is responsible for metabolising anywhere from 45-60% of prescribed medications.

However, different supplements and foods can impact the way in which this enzyme works, and CBD is one of them.

If you’re considering taking CBD oil for your condition, it’s important to discuss any other medications with an authorised prescriber.

Let’s explore the science a little further.

Metabolisation

Metabolisation is the process that your body uses to break down substances and remove them from your system.

If metabolisation happens too slowly, then medication can build up in your system faster than your body removes it. This can result in higher dosages in your body than intended, causing unwanted or harmful side effects.

If metabolisation happens too quickly, then your body may break down medications too quickly.

When this happens, not enough of the medication will stay in your system for long enough to treat your health issue.

About 60% of all clinically prescribed medications rely on the normal metabolisation rate of the CYP3A4 enzyme. As a result, consuming substances that interact with the CYP3A4 enzyme or its production may interfere with some medications. [1]

This effect also works in reverse. In other words, taking medications that inhibit the CYP3A4 enzyme can reduce the effects of CBD.

CBD Is A CYP3A4 Inhibitor

Cannabidiol is a CYP3A4 inhibitor, which means that it reduces the amount of CYP3A4 enzyme that is available in your system to metabolise other compounds.

CBD does not affect the production of the CYP3A4 enzyme or its function, rather, the body utilises this enzyme to break down CBD supplements that have been consumed. [2]

There is only a certain amount of CYP3A4 enzyme available in your system at any given time. If there is a significant amount of CBD in your body, there are fewer enzyme molecules able to break down other compounds at the usual rate.

As a result, CBD inhibits the efficacy of the CYP3A4 enzyme while it remains in your system.

Using it while taking certain medications could cause more of that medication to build up in your system.

Because of this concern, you should always talk to your doctor about interactions with your other medications before starting to use any CBD product.

What Are CYP3A4 Inhibitors Used For?

CYP3A4 inhibitors are sometimes prescribed to help control the levels of a drug that is metabolised by CYP3A4 in your system.

For example, cyclosporine is a drug that is used to prevent your body from rejecting organ transplants. In some people, cyclosporine can be metabolised so quickly that it does not achieve the intended immunosuppressant effect.

A CYP3A4 inhibitor such as ketoconazole or diltiazem may be prescribed in these cases to slow down how quickly cyclosporine is metabolised. [3]

CYP3A4 Inhibitors List

All of the following medications can have inhibiting effects on the CYP3A4 enzyme: [4]

  • Cimetidine
  • Amiodarone
  • Erythromycin
  • Fluconazole
  • Miconazole
  • Diltiazem
  • Verapamil
  • Delavirdine
  • Amprenavir
  • Fosamprenavir
  • Conivaptan

What About CYP3A4 Inducers?

CYP3A4 inhibitors are not the only type of compound that can affect the CYP3A4 enzyme.

CYP3A4 inducers have the opposite effect as inhibitors. An enzyme inducer instead increases the metabolisation rate of the enzyme by binding to enzyme molecules and activating them. This causes the enzyme to break down compounds faster.

Some medications contain CYP3A4 inducers in order to speed up the metabolisation of certain compounds, preventing an unsafe build-up in your system.

How Does CBD Affect CYP3A4 Inducers?

CBD inhibits the efficacy of the CYP3A4 enzyme in your system, while CYP3A4 inducers increase their metabolisation. So what happens if you take CBD and an inducer at the same time?

The reality is that there is a lot we just don’t know yet about how CBD interacts with different medications. As a result, it may have interactions with CYP3A4 inducers, and the enzyme itself, that we don’t know about yet.

However, two key assumptions can be made as they are true of the interactions between all enzyme inducers and inhibitors:

  1. Firstly, the increased metabolisation caused by the CYP3A4 inducer could mean that CBD stays in your system for a shorter period of time, having less of an effect on you.
  2. Secondly, though it may have a reduced effect thanks to the inducer, CBD will still inhibit the CYP3A4 enzyme. Other medications could still take longer to be broken down than usual, possibly resulting in unwanted side effects.

A doctor at a desk fills out a report next to CBD oil bottles

Known CBD Drug Interactions

Research into the effects of CBD on different drugs is still ongoing. This can make it hard to know whether you can safely take CBD while on prescribed medications.

Here is a tip to help you out:

Grapefruit contains chemicals called furanocoumarins, which are major CYP3A4 inhibitors that can cause an unsafe build-up of certain drugs.

As a result, medications that rely on the CYP3A4 enzyme for metabolisation often feature a warning to avoid grapefruit or grapefruit juice. If you see this warning, CBD could also interfere with the drug too.

So far, researchers have identified at least 139 medications that could be affected by CBD.

However, this may not be dangerous in all cases. On this list of 139 drugs, only 57 of them saw an unsafe concentration of the drug as a result of taking CBD. [5]

This means that taking CBD while using these medications might be safe for some people. For example, a small study investigated the effects of CBD on commonly used anti-epilepsy drugs and found that only 2 drugs, clobazam and desmethylclobazam, built up to unsafe levels in the presence of CBD. [6]

Can You Take CBD With CYP3A4 Inducers?

With the wide array of CBD products popping up online, such as CBD-infused honey and CBD jelly beans, it may seem fairly straightforward to consume these tasty treats, but taking CBD could lead to a build-up of certain medications in your system, even if you are taking a CYP3A4 inducer.

It may be possible to find a balance depending on your situation, but you should always talk to your doctor before taking CBD if you take any other medications.

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References

1. Shufeng Zhou et al., "Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4 ".
National Library of Medicine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661603/.
2. Satoshi Yamaori et al., "Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiet".
National Library of Medicine.
https://pubmed.ncbi.nlm.nih.gov/21356216.
3. Chris Ogu and Jan Maxa, "Drug interactions due to cytochrome P450".
National Library of Medicine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312247/.
4. Anthony Busti, "Common Medications Classified as Weak, Moderate and Strong Inhibitors of CYP3A4".
EBM Consult.
https://www.ebmconsult.com/articles/medications-inhibitors-cyp3a4-enzyme.
5. N/A, "NTI Meds to be Closely Monitored when Co-Administered with Cannabinoids".
Pennsylvania State University.
https://sites.psu.edu/cannabinoid/files/2020/06/NTI-Meds-to-be-Closely-Monitored-when-Co-Administered-with-Cannabinoids_2020_04_25.pdf.
6. Lyndsey L. Anderson et al., "Interactions between cannabidiol and commonly used antiepileptic drug".
Epilepsia.
https://onlinelibrary.wiley.com/doi/10.1111/epi.13852.

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Disclaimer. While we strive to relay the most factual education available, this shouldn’t replace official medical or legal consultation and recommendation. This is for educational and entertainment purposes only. Happy days.

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