CBD Oil Drug Interactions

The pharmacist discusses potential interactions with CBD (cannabidiol).

Question

There is a lot of information I have been reading about CBD but I am curious about drug interactions. Are you able to give me a run down of serious interactions if I were to use a CBD oil?

Asked by Joe On Nov 09, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Nov 09, 2018
CBD Title 3

Overview

There are several potential drug interactions with CBD (cannabidiol) but many of them aren't well studied.

Currently, the most well known interactions are with:

  • Certain anti-epileptic drugs (e.g. Depakote, Onfi)
  • Drugs metabolized via CYP3A4
  • Drugs metabolized via CYP2C19
  • CNS depressants and alcohol

Below, we describe these interactions and other potential conflicts with CBD.

If you are looking to check specific interactions with CBD, be sure to use our drug interaction checker:


What Is CBD?

CBD Image

Cannabidiol often referred to simply as 'CBD', is a non-psychoactive constituent of marijuana. Unlike THC, CBD is not known to cause euphoria but does affect the central nervous system as studies show it can be beneficial for symptoms of anxiety and can cause sedation.

CBD is known to have significant activity within the endocannabinoid system and has been studied for a wide variety of therapeutic effects, including for the treatment of:

  • Chronic Pain
  • PTSD
  • Multiple sclerosis
  • Parkinson's Disease
  • Epilepsy
  • Huntington's Disease

In addition, CBD may make high THC preparations more tolerable for individuals as it can 'attenuate' or reduce the 'high' experienced.

CBD is a popular over the counter supplement and is also available as the prescription product Epidiolex, which is approved for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older.

CBD is reported to be generally well-tolerated, and side effects, if they occur, tend to be mild. Nevertheless, CBD can cause:

  • Sedation
  • Dizziness
  • Diarrhea
  • Changes in appetite/weight
  • Dry mouth
  • Lightheadedness

CBD With Anti-Epileptic Drugs

Pills In Cap

The prescribing information for Epidiolex, a prescription CBD (cannabidiol) product, discusses interactions with two specific anti-epileptic drugs:

  • Depakote (Valproic Acid)
  • Onfi (Clobazam)

Depakote (Valoproic Acid)

Studies indicate that CBD and valproate products (e.g. Depakote) can increase liver enzymes, potentially increasing the risk of liver damage. Per the prescribing information for Epidiolex:

"Concomitant use of EPIDIOLEX and valproate increases the incidence of liver enzyme elevations. Discontinuation or reduction of EPIDIOLEX and/or concomitant valproate should be considered. Insufficient data are available to assess the risk of concomitant administration of other hepatotoxic drugs and EPIDIOLEX"


Onfi (Clobazam)

CBD can potentially increase levels of Onfi (clobazam), increasing the risk of side effects. Again, per the prescribing information for Epidiolex:

"Coadministration of EPIDIOLEX produces a 3-fold increase in plasma concentrations of Ndesmethylclobazam, the active metabolite of clobazam (a substrate of CYP2C19). This may increase the risk of clobazam-related adverse reactions. Consider a reduction in dosage of clobazam if adverse reactions known to occur with clobazam are experienced when co-administered with EPIDIOLEX."

CBD With CYP3A4/CYP2C19

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CBD (cannabidiol) is known to be metabolized by the metabolizing enzymes CYP3A4 and CYP2C19. Drugs that either inhibit or induce CYP3A4 or CYP2C19 could potentially affect how CBD is metabolized in the body.

The prescribing information for Epidiolex (cannabidiol) states the following regarding these enzymes:

"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. Consider a reduction in EPIDIOLEX dosage when coadministered with a moderate or strong inhibitor of CYP3A4 or CYP2C19. Strong CYP3A4 or CYP2C19 Inducers Coadministration with a strong CYP3A4 or CYP2C19 inducer will decrease cannabidiol plasma concentrations, which may lower the efficacy of EPIDIOLEX. Consider an increase in EPIDIOLEX dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 or CYP2C19 inducer."

As stated above, co-administration with a moderate or strong inhibitor of CYP3A4 can potentially increase CBD (cannabidiol) plasma concentrations, which may result in a greater risk of side effects.

Known strong inhibitors of CYP3A4 include:

Co-administration with a moderate or strong inducer of CYP3A4 can potentially decrease cannabidiol plasma concentrations, which may result in a lowered therapeutic effect:

Known strong inducers of CYP3A4 include:

In the same respect as CYP3A4, co-administration with a moderate or strong inhibitor of CYP2C19 could increase cannabidiol plasma concentration. Co-administration with a strong inducer could decrease CBD (cannabidiol) concentrations.

Known CYP2C19 inhibitors include:

Known CYP2C19 inducers include:

  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Rifampin
  • St. John’s wort

There haven't been studies evaluating potential interactions with all the above drugs. They are more theoretical based on what we know about how they are metabolized and how they affect drug metabolism.


Other CBD Interactions

In addition to the potential interactions listed above, CBD may also interact with:

  • CYP1A2 substrates (e.g., theophylline, caffeine)
  • CYP2B6 substrates (e.g., bupropion, efavirenz)
  • Uridine 5' diphospho-glucuronosyltransferase 1A9 (UGT1A9) substrates (e.g., diflunisal, propofol, fenofibrate)
  • UGT2B7 substrates (e.g., gemfibrozil, lamotrigine, morphine, lorazepam)
  • CNS depressants (e.g. alcohol)

The above aren't thought to be as significant as the potential CYP3A4/CYP2C19 interactions but are important to be aware of nonetheless.


Final Words

It is important to check into potential drug interactions if you are considering using CBD oil. Even though CBD is a 'natural' supplement, it still has potentially serious drug interactions.

Be sure to ask your local pharmacist or doctor about using CBD with your current medications.


Summary

CBD (cannabidiol) can potentially interact with several medications, including several anti-epileptic drugs (e.g. Onfi) and those that affect CYP metabolizing enzymes (e.g. CYP3A4, CYP2C19).

References
  1. Epidiolex Prescribing Information. AccessFDA
  2. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. AccessFDA
  3. Overview of Efficacy and Safety of Cannabidiol in Patients with Lennox-Gastaut Syndrome and Dravet Syndrome. FDA
  4. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. PubMed
  5. Controlled clinical trial of cannabidiol in Huntington's disease. PubMed
  6. Cannabidiol for the treatment of psychosis in Parkinson's disease. PubMed
  7. Oromucosal Δ9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: An uncontrolled, open-label, 2-year extension trial. ScienceDirect
  8. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. The Royal Society
  9. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems. JAMA
  10. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. PubMed
  11. Effects of ipsapirone and cannabidiol on human experimental anxiety. PubMed

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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