Amiodarone CBD Title Card

Yes, there is a potential interaction between CBD (cannabidiol) and amiodarone. However, it hasn't been well-documented or studied and the potential severity isn't known.

Having said that, there is a good amount of published data on both CBD and amiodarone that gives us a good idea of how they could interact with each other.

Amiodarone is notorious for having several major drug interactions, simply based on how it is affects metabolizing enzymes and the liver.

Being an anti-arrhythmic medication, it is extremely important that amiodarone is dosed correctly. Taking it with other medications that could alter concentrations of it in the body can be dangerous (i.e. by increasing the risk of side effects or decreasing effectiveness).

I discuss the potential interaction in more detail in the next sections but it important to make the overall point that you shouldn't use CBD (cannabidiol) with amiodarone without speaking to your doctor first.

Amiodarone Metabolism

Amiodarone is class III antiarrhythmic drug, has a complex pharmacokinetic profile, and is metabolized via a variety of pathways in the body.

Several studies have been published on the pharmacokinetic profile of amiodarone, which is important when it comes to potential drug interactions.

It is extensively metabolized in the liver, mostly by two enzymes:

  • CYP3A4
  • CYP2C8

CBD (Cannabidiol) Interacting With Amiodarone

Any drug that affects those enzymes (either by inhibiting or inducing them), can alter concentrations of amiodarone in the body. This has the potential to increase the risk of severe side effects/toxicity or decrease the effectiveness of the drug, both serious consequences.

The prescribing information warns about taking amiodarone with CYP3A4 or CYP2C8 inhibitors:

"Since amiodarone is a substrate for CYP3A4 and CYP2C8, drugs/substances that inhibit CYP3A4 may decrease the metabolism and increase serum concentrations of amiodarone."

Numerous studies have reported that CBD (cannabidiol) can inhibit CYP2C8. In fact, the prescribing information for Epidiolex, a prescription CBD product used for treating a rare form of seizures (Lennox-Gastaut syndrome or Dravet syndrome) states the following:

"Coadministration of EPIDIOLEX [cannabidiol] is also predicted to cause clinically significant interactions with CYP2C8 and CYP2C9 (e.g., phenytoin) substrates."

The prescribing information goes on to say that dose adjustments for certain drugs (i.e. for amiodarone) may be necessary due to the fact that Epidioldex (cannabidiol) can alter concentrations of them via enzyme inhibition.

Amiodarone Interacting With CBD

Not only can CBD (cannabidiol) change amiodarone concentrations due to inhibition of metabolizing enzymes (mainly CYP2C8), amiodarone is a strong inhibitor of CYP3A4.

The prescribing information for amiodarone states:

Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A4. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates of p-glycoprotein

The metabolism of CBD is complex, but studies show that it is at least partially metabolized by CYP3A4. If CYP3A4 activity is inhibited (such as by amiodarone), metabolism may decrease, which can increase CBD concentrations.

Again, per the prescribing information for Epidiolex (cannabidiol):

EPIDIOLEX is metabolized by CYP3A4 and CYP2C19. Therefore, coadministration with a moderate or strong inhibitor of CYP3A4 or CYP2C19 will increase cannabidiol plasma concentrations, which may result in a greater risk of adverse reactions

Amiodarone is one of the strongest known inhibitors of CYP3A4, so it may very well increase concentrations in the body of CBD if taken together.

Liver Enzymes

Another potential issue with taking amiodarone with CBD is that both have been shown to cause abnormal elevations in liver enzymes (which is in addition to changes to metabolizing enzymes).

For both drugs, before starting treatment, it is recommended to test liver enzymes and monitor periodically throughout treatment. It is especially important to monitor liver enzymes if you are taking more than one drug associated with liver injury (like amiodarone and CBD).

Answer Summary

CBD (cannabidiol) and amiodarone can interact via a variety of mechanisms. Taking them together can increase concentrations of both, increasing the risk of side effects. Additionally, they can both cause elevated liver enzymes. Therefore, they should not be used together unless directed by your doctor.