One of the oft-asked questions in regards to health and pharmaceuticals is whether or not cannabis can be mixed with medication. It is, indeed, a valid concern to raise, especially for those who regularly take cannabidiol for whatever purpose. It is understandable to argue in support of it, especially when it comes to CBD oil. After all, “it's non-psychotropic and bears therapeutic potential, so it must be safe, right?”.

Well, in case you didn't know, the cannabis plant contains over a hundred chemical compounds. On their own, these compounds react safely with one another. But the question is, will it be the same when it comes to interacting with other drugs?

This article should provide you with a clear answer, once and for all. Hopefully, the information will be helpful for you down the line.

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Can CBD Oil Affect Medication?

Before answering this, let’s first address another important question: how exactly does CBD interact with our bodies?

The simple answer: CBD interfaces with receptors in the endocannabinoid system—CB1 and CB2—among other molecular targets, including serotonin and vanilloid receptors. Intriguingly, CBD hinders the breakdown of certain chemicals—including anandamide—that directly affect our mood, pain perception, and mental function.

In doing so, CBD is able to sustain higher levels of these beneficial chemicals in the body, promoting overall homeostasis (dynamic balance) between our physiological systems.

However, CBD also affects the metabolism of medications, a process that takes place primarily in the liver.

How Does the Body Metabolise CBD?

Cannabinoids, including CBD, are metabolised by the liver with the help of cytochrome P450 enzymes. CBD is then broken down and distributed throughout the entire body, where it can get to work promoting balance.

CBD can remain in the body for about four weeks. During that time, it is stored within fatty tissues until it is gradually released in small doses back into the bloodstream. From there, cannabidiol is metabolised through the renal (aka urinary) and biliary systems of the body.

Now, we mentioned cytochrome P450 enzymes and the vital role they play in metabolising CBD. But, what are they exactly?

How Does the Body Metabolise CBD?

What Is the Cytochrome P450 System?

CBD’s drug interactions largely stem from the cytochrome P450 system. This group of liver enzymes is mainly responsible for breaking down toxins, drugs, and other foreign substances in our system. These enzymes basically dissect these substances to make them easier to eliminate from the body.

But, when CBD enters the party, the liver stops metabolising other drugs that rely on cytochrome P450 enzymes, and shifts its attention to CBD.

In some cases, CBD can completely deactivate cytochrome P450 activity, albeit temporarily, which can affect the metabolic activity of compounds found in certain drugs. So, for example, if you’re taking a powerhouse painkiller like oxycodone alongside cannabidiol, the former may linger in your system for longer—which isn’t necessarily a good thing.

What can be problematic is that a drug like oxycodone is only supposed to stay in your system for a certain period of time. Going beyond that duration may elicit side effects like nausea and drowsiness, which could be an issue if you’re driving a car or operating heavy machinery. At worst, it can cause liver damage.

Drugs CBD Oil Can Interact With

The fact of the matter is, cytochrome P450 enzymes metabolise around 90%[1] of all medications on the market, with two enzymes in particular—CYP3A4 and CYP2D6—being responsible for the lion’s share of the work. So, here’s the simple answer: any drug metabolised by cytochrome P450 enzymes will interact with CBD oil. Some of these drug interactions will bear no adverse effects, while others will.

Let’s get a little more specific. A 2016 study[2] delved into how CBD reacted with a known anti-seizure medication called clobazam, which is largely used to treat epilepsy among children. This interaction is particularly intriguing, as CBD (in synthetic form, "Epidiolex") has also been approved for treatment-resistant forms of Lennox–Gastaut syndrome and Dravet syndrome.

The study found that cannabidiol slowed down the metabolism of clobazam, which led to a significant increase in plasma levels of medication in the body—around 60–80%. As a result, researchers were able to lower the dose of clobazam administered to the subjects, without sacrificing efficacy. Even more interesting, the drug’s side effects, like insomnia, loss of coordination, drowsiness, and constipation, were all curbed with this lower dose.

Here’s a list of other drugs, their classification, and how CBD interacts with them. Also included are some expert recommendations on whether or not cannabidiol should be used.

Drugs CBD Oil Can Interact With

  • CYP3A4 Substrates

Substrates are essentially drugs that are metabolised by cytochrome P450 enzymes. CYP3A4, specifically, is an enzyme in the liver and intestines that oxidises toxins or drugs for easier excretion from the body.

Immunosuppressants and antidepressants belong to this category, alongside antipsychotics, calcium channel blockers, and opioids. Also part of this list of medications are benzodiazepines, z-hypnotics, statins, and chemotherapeutics.

Depending on the drug, the risk of side effects may be increased. As recommended by experts, co-administration with CBD isn’t advised. Doses must also be altered accordingly, and the potential for adverse effects and toxicity should be monitored.

Prescription cascade, known as the misdiagnosis of drug side effects as symptoms, must be highly avoided. This should also help reduce side effects in turn.

List of medications
Carbamazepine Felbamate
Phenytoin Ethosuximide
Phenobarbital Tiaagabine
Zonisamide

  • CYP34 Inhibitors

Protease inhibitors are antiviral drugs that are usually prescribed to patients diagnosed with HIV. Loperamide, on the other hand, is a medication used for instant diarrhoea treatment.

These drugs are examples of CYP34 inhibitors, and they are quite similar to their substrate counterparts.

When CBD interacts with any of these drugs, its bioavailability—or the percentage of its dose that enters the body upon administration—tends to increase. As a result, the risk of adverse effects may increase.

Experts don’t necessarily advise against taking CBD alongside these medications, but a reduced dose is recommended.

Protease inhibitors and loperamide are examples of stronger CYP34 inhibitors. The more moderate ones are amiodarone, verapamil, aprepitant, and cimetidine.

List of medications
Allopurinol Fluconazole
Amiodarone Fluoxetine
Amprenavir Quinolones
Aprepitant Valproic acid
Atazanavir Grapefruit juice
Chloramphenicol Imatinib
Cimetidine Indinavir
Clarithromycin Isoniazid
Nifedipedine Itraconazole
Tamoxifen Ketoconazole
Cyclosporine Nefazodone
Darunavir Nelfinavir
Dasatinib Ritonavir
Delavirdine Verapamil
Diltiazem Saquinavir
Erythromycin
  • CYP3A4 Inducers

Phenobarbitals are medications used to treat people suffering from seizures. In some cases, they can also be used as a mild, short-term sedative. Enzalutamide, on the other hand, is used for prostate cancer treatment. It is a hormone blocker that prevents testosterone from reaching prostate cancer cells.

These drugs are examples of CYP3A4 inducers. Unlike inhibitors, upon interacting with these drugs, CBD’s bioavailability, along with its effectiveness, decreases. In this case, increasing cannabidiol dose is recommended.

Other examples of CYP3A4 inducers are phenytoin, carbamazepine, topiramate, rifampicin, and pioglitazone.

List of medications
Carbamazepine Omeprazole
Corticosteroids Rifampin
Efavirenz Oxacarbazepine
Rifabutin Phenytoin
Modafinil Primidone
Nevirapine St. John's wort

  • CYP2C19 Substrates

CYP2C19 enzymes activate the metabolic process for xenobiotics like anti-seizure medications. And, like CYP34 substrates, they carry the same side effects when mixed with CBD.

Similarly, co-administration with cannabidiol isn’t advised, and adverse effects and toxicity need to be monitored closely. Prescription cascade should also be avoided.

Other examples of CYP2C19 substrates are proton pump inhibitors, antidepressants, clopidogrel, carisoprodol, and warfarin.

List of medications
Aripiprazole (Abilify) Lansoprazole (Prevacid)
Carisoprodol (Soma) Mephenytoin (Mesantoin)
Citalopram (Celexa) Methadone
Clomipramine (Anafranil) Propranolol
Clopidogrel (Plavix) Voriconazole (Vfend)
Clozapine (Clozaril) R-warfarin
Desipramine (Norpramin) Moclobemide (Manerix)
Diazepam (Valium) Nelfinavir (Viracept)
Sertraline (Zoloft) Olanzapine (Zyprexa)
Thalidomide Omeprazole (Prilosec)
Proguanil Pantoprazole (Protonix)
Diphenhydramine (Benadryl) Pentamidine
Doxepin (Sinequan) Phenobarbital
Escitakopram (Lexapro) Phenytoin
Fluoxertine (Prozac) Rabeprazole
Imipramine (Tofranil)
  • CYP2C19 Inhibitors

Those who use Prozac are very familiar with fluoxetine. It is used to treat specific mental conditions like depression and even bulimia. Similarly, fluvoxamine is an antidepressant that is mainly used by people with obsessive-compulsive disorder.

These two drugs are primary examples of CYP2C19 inhibitors. As it is with these medications, CBD’s bioavailability increases upon interaction. The risk of adverse effects may increase as a result, which is why lower CBD doses are advised.

Other drugs that fall under the CYP2C19 inhibitor category are efavirenz, fluconazole, ketoconazole, and clopidogrel.

List of medications
Chloramphenicol Isoniazid
Cimetidine (Tagamet) Moclobemide (Manerix)
Clopidogrel (Plavix) Modafinil (Provigil)
Delavirdine (Rescriptor) Omeprazole (Priosec)
Efavirenz (Sustiva) Oxcarbazepine (Trileptal)
Esomeprazole (Nexium) Ticlopidine (Ticlid)
Felbamate (Felbatol) Voriconazole (Vfend)
Fluconazole (Prozac) Fluconazole (Diflucan)
Fluvoxamine
  • CYP2C19 Inducers

Tuberculosis patients will be greatly familiar with rifampin. It’s an oral medication used as an antibiotic to treat bacterial complications. Meanwhile, carbamazepine is an anticonvulsant used to treat seizures and schizophrenia.

These two drugs are the best examples of CYP2C19 inducers. They’re relatively safe when taken with CBD because, unlike inhibitors, the bioavailability of the cannabinoid decreases upon interaction, resulting in a reduction in effectiveness. Experts recommend an increase in CBD dose when co-administering with CYP2C19 inducers.

Other drugs that belong to this category are phenytoin, phenobarbital, and St. John’s wort.

List of medications
Aminoglutethimide Primidone
Artemisinin Rifampin
Barbiturates Rifapentine
Carbamazepine St. John's wort
Phenytoin

  • CYP2C8/9 Substrates

Both CYP2C8 and CYP2C9 enzymes are directly responsible for metabolising xenobiotics. However, the former can also metabolise polyunsaturated fatty acids.

And, because it is a substrate, there is an increased risk of side effects. Co-administration with CBD isn’t advised, and lower substrate doses are recommended.

A good example of a CYP2C8 and CYP2C9 substrate is rosiglitazone, a medication for type 2 diabetes. Antihypertensive drug losartan is also part of this list, along with naproxen, celecoxib, rosuvastatin, and sulfonylureas—just to name a few.

List of medications
Amiodarone (Cordarone) Carbamazepine (Tegretol)
Diclofenac (Voltaren) Paclitaxel (Taxol)
Repaglinide (Prandin) Cabazitaxel (Jevtana)
Chloroquine (Aralen) Ibuprofen (Advil)
Rosiglitazone (Avandia) Treprostinil (Tyvaso)

What Is the Grapefruit Test?

You’ve probably seen the “grapefruit warning” on some of your medications. If you’re taking one of these drugs, you’re advised to avoid consuming any grapefruit. But why is that?

Like CBD, grapefruit also inhibits cytochrome P450 enzymes, which directly affects the metabolism of these substances. That means consuming grapefruit could ramp up the dose of the drug in the bloodstream, which may result in an overdose.

Research shows that more than 85 drugs[3] share this same interaction with grapefruit. Among them are fentanyl, erythromycin, losartan, loratadine, and alprazolam.

If in Doubt, Speak to Your Doctor

So, with all the hype behind it, is it safe to take CBD oil while on medication? If you’ve read through the entire article, the most logical answer would be: it depends on what you are taking.

You know your body better than anyone else, so you should be able to monitor how CBD oil affects your regular medication routine. Just make sure to pay close attention, and, most importantly, take everything in moderation. Nothing good ever came out of excessive use.

But, if you want to be on the safest side, ask your doctor. They can speak to you in lay terms about the effects of these drugs and how CBD may interact with them. This is the best way to obtain sound advice and answers to any questions you may have.

Medical DisclaimerInformation listed, referenced or linked to on this website is for general educational purposes only and does not provide professional medical or legal advice.

Royal Queen Seeds does not condone, advocate or promote licit or illicit drug use. Royal Queen Seeds Cannot be held responsible for material from references on our pages or on pages to which we provide links, which condone, advocate or promote licit or illicit drug use or illegal activities. Please consult your Doctor/Health care Practitioner before using any products/methods listed, referenced or linked to on this website.

External Resources:
  1. The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects - American Family Physician https://www.aafp.org
  2. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy https://www.ncbi.nlm.nih.gov
  3. Common Grapefruit Juice Drug Interactions - Drugs.com https://www.drugs.com
Disclaimer:
This content is for educational purposes only. The information provided is derived from research gathered from external sources.

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