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cbd interactions

Cannabidiol (CBD)

What is it?

Cannabidiol is a chemical in the Cannabis sativa plant, also known as marijuana or hemp. Over 80 chemicals, known as cannabinoids, have been identified in the Cannabis sativa plant. While delta-9-tetrahydrocannabinol (THC) is the major active ingredient in marijuana, cannabidiol is also obtained from hemp, which contains only very small amounts of THC.

The passage of the 2018 Farm Bill made it legal to sell hemp and hemp products in the U.S. But that doesn’t mean that all hemp-derived cannabidiol products are legal. Since cannabidiol has been studied as a new drug, it can’t be legally included in foods or dietary supplements. Also, cannabidiol can’t be included in products marketed with therapeutic claims. Cannabidiol can only be included in “cosmetic” products and only if it contains less than 0.3% THC. But there are still products labeled as dietary supplements on the market that contain cannabidiol. The amount of cannabidiol contained in these products is not always reported accurately on the product label.

Cannabidiol is most commonly used for seizure disorder (epilepsy). It is also used for anxiety, pain, a muscle disorder called dystonia, Parkinson disease, Crohn disease, and many other conditions, but there is no good scientific evidence to support these uses.

How effective is it?

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

The effectiveness ratings for CANNABIDIOL (CBD) are as follows:

Likely effective for.

  • Seizure disorder (epilepsy). A specific cannabidiol product (Epidiolex, GW Pharmaceuticals) has been shown to reduce seizures in adults and children with various conditions that are linked with seizures. This product is a prescription drug for treating seizures caused by Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. It has also been shown to reduce seizures in people with Sturge-Weber syndrome, febrile infection-related epilepsy syndrome (FIRES), and specific genetic disorders that cause epileptic encephalopathy. But it’s not approved for treating these other types of seizures. This product is usually taken in combination with conventional anti-seizure medicines. Some cannabidiol products that are made in a lab are also being studied for epilepsy. But research is limited, and none of these products are approved as prescription drugs.

Insufficient evidence to rate effectiveness for.

  • A type of inflammatory bowel disease (Crohn disease). Early research shows that taking cannabidiol does not reduce disease activity in adults with Crohn disease.
  • Diabetes. Early research shows that taking cannabidiol does not improve blood glucose control adults with type 2 diabetes.
  • A movement disorder marked by involuntary muscle contractions (dystonia). It is unclear if cannabidiol is beneficial for dystonia.
  • An inherited condition marked by learning disabilities (fragile- X syndrome). Early research suggests that applying cannabidiol gel might reduce anxiety and improve behavior in children with fragile X syndrome.
  • A condition in which a transplant attacks the body (graft-versus-host disease or GVHD). Graft-versus-host disease is a complication that can occur after a bone marrow transplant. Early research has found that taking cannabidiol daily starting 7 days before bone marrow transplant and continuing for 30 days after transplant can extend the time it takes for a person to develop GVHD.
  • An inherited brain disorder that affects movements, emotions, and thinking (Huntington disease). Early research shows that taking cannabidiol daily does not improve symptoms of Huntington disease.
  • Multiple sclerosis (MS). Early research suggests that using a cannabidiol spray under the tongue might improve pain and muscle tightness in people with MS.
  • Withdrawal from heroin, morphine, and other opioid drugs. Early research shows that taking cannabidiol for 3 days might reduce cravings and anxiety in people with heroin use disorder.
  • Parkinson disease. Early research shows that cannabidiol might reduce anxiety and psychotic symptoms in people with Parkinson disease.
  • Schizophrenia. Early research suggests that taking cannabidiol improves symptoms and wellbeing in people with schizophrenia.
  • Quitting smoking. Early research suggests that inhaling cannabidiol with an inhaler for one week might reduce the number of cigarettes smoked by smokers trying to quit.
  • A type of anxiety marked by fear in some or all social settings (social anxiety disorder). Early research shows that cannabidiol might improve anxiety in people with this disorder. But it’s unclear if it helps reduce anxiety during public speaking.
  • A group of painful conditions that affect the jaw joint and muscle (temporomandibular disorders or TMD). Early research shows that applying an oil containing cannabidiol to the skin might reduce pain in people with TMD.
  • Nerve damage in the hands and feet (peripheral neuropathy).
  • Bipolar disorder.
  • Insomnia.
  • Other conditions.

More evidence is needed to rate the effectiveness of cannabidiol for these uses.

How does it work?

Cannabidiol has effects on the brain. The exact cause for these effects is not clear. However, cannabidiol seems to prevent the breakdown of a chemical in the brain that affects pain, mood, and mental function. Preventing the breakdown of this chemical and increasing its levels in the blood seems to reduce psychotic symptoms associated with conditions such as schizophrenia. Cannabidiol might also block some of the psychoactive effects of delta-9-tetrahydrocannabinol (THC). Also, cannabidiol seems to reduce pain and anxiety.

Are there safety concerns?

When taken by mouth: Cannabidiol is POSSIBLY SAFE when taken by mouth or sprayed under the tongue appropriately. Cannabidiol in doses of up to 300 mg daily have been taken by mouth safely for up to 6 months. Higher doses of 1200-1500 mg daily have been taken by mouth safely for up to 4 weeks. A prescription cannabidiol product (Epidiolex) is approved to be taken by mouth in doses of up to 25 mg/kg daily. Cannabidiol sprays that are applied under the tongue have been used in doses of 2.5 mg for up to 2 weeks.

Some reported side effects of cannabidiol include dry mouth, low blood pressure, light headedness, and drowsiness. Signs of liver injury have also been reported in some patients, but this is less common.

When applied to the skin: There isn’t enough reliable information to know if cannabidiol is safe or what the side effects might be.

Special precautions & warnings:

Pregnancy and breast-feeding: Cannabidiol is POSSIBLY UNSAFE to use if you are pregnant or breast feeding. Cannabidiol products can be contaminated with other ingredients that may be harmful to the fetus or infant. Stay on the safe side and avoid use.

Children: A prescription cannabidiol product (Epidiolex) is POSSIBLY SAFE when taken by mouth in doses up to 25 mg/kg daily. This product is approved for use in certain children 1 year of age and older.

Liver disease: People with liver disease may need to use lower doses of cannabidiol compared to healthy patients.

Parkinson disease: Some early research suggests that taking high doses of cannabidiol might make muscle movement and tremors worse in some people with Parkinson disease.

Are there interactions with medications?

Moderate Be cautious with this combination. Brivaracetam (Briviact) Brivaracetam is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down brivaracetam. This might increase levels of brivaracetam in the body. Carbamazepine (Tegretol) Carbamazepine is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down carbamazepine. This might increase levels of carbamazepine in the body and increase its side effects. Clobazam (Onfi) Clobazam is changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down clobazam. This might increase the effects and side effects of clobazam. Eslicarbazepine (Aptiom) Eslicarbazepine is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down eslicarbazepine. This might increase levels of eslicarbazepine in the body by a small amount. Everolimus (Zostress) Everolimus is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down everolimus. This might increase levels of everolimus in the body. Lithium Taking higher doses of cannabidiol might increase levels of lithium. This can increase the risk of lithium toxicity. Medications changed by the liver (Cytochrome P450 1A1 (CYP1A1) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include chlorzoxazone (Lorzone) and theophylline (Theo-Dur, others). Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include amitriptyline (Elavil), haloperidol (Haldol), ondansetron (Zofran), propranolol (Inderal), theophylline (Theo-Dur, others), verapamil (Calan, Isoptin, others), and others. Medications changed by the liver (Cytochrome P450 1B1 (CYP1B1) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include theophylline (Theo-Dur, others), omeprazole (Prilosec, Omesec), clozapine (Clozaril, FazaClo), progesterone (Prometrium, others), lansoprazole (Prevacid), flutamide (Eulexin), oxaliplatin (Eloxatin), erlotinib (Tarceva), and caffeine. Medications changed by the liver (Cytochrome P450 2A6 (CYP2A6) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include nicotine, chlormethiazole (Heminevrin), coumarin, methoxyflurane (Penthrox), halothane (Fluothane), valproic acid (Depacon), disulfiram (Antabuse), and others. Medications changed by the liver (Cytochrome P450 2B6 (CYP2B6) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include ketamine (Ketalar), phenobarbital, orphenadrine (Norflex), secobarbital (Seconal), and dexamethasone (Decadron). Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include proton pump inhibitors including omeprazole (Prilosec), lansoprazole (Prevacid), and pantoprazole (Protonix); diazepam (Valium); carisoprodol (Soma); nelfinavir (Viracept); and others. Medications changed by the liver (Cytochrome P450 2C8 (CYP2C8) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications changed by the liver include amiodarone (Cordarone), carbamazepine (Tegretol), chloroquine (Aralen), diclofenac (Voltaren), paclitaxel (Taxol), repaglinide (Prandin) and others. Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), piroxicam (Feldene), and celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar); and others. Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others. Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include alprazolam (Xanax), amlodipine (Norvasc), clarithromycin (Biaxin), cyclosporine (Sandimmune), erythromycin, lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), verapamil (Calan, Isoptin) and many others. Medications changed by the liver (Cytochrome P450 3A5 (CYP3A5) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications changed by the liver include testosterone, progesterone (Endometrin, Prometrium), nifedipine (Adalat CC, Procardia XL), cyclosporine (Sandimmune), and others. Medications changed by the liver (Glucuronidated drugs) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. Taking cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of these medications.
Some of these medications changed by the liver include acetaminophen (Tylenol, others) and oxazepam (Serax), haloperidol (Haldol), lamotrigine (Lamictal), morphine (MS Contin, Roxanol), zidovudine (AZT, Retrovir), and others. Medications that decrease the breakdown of other medications by the liver (Cytochrome P450 2C19 (CYP2C19) inhibitors) Cannabidiol is broken down by the liver. Some medications might decrease how quickly the liver breaks down cannabidiol. Taking cannabidiol along with these medications might increase the effects and side effects of cannabidiol.
Some medications that might decrease the breakdown cannabidiol in the liver include cimetidine (Tagamet), fluvoxamine (Luvox), omeprazole (Prilosec); ticlopidine (Ticlid), topiramate (Topamax), and others. Medications that decrease the breakdown of other medications in the liver (Cytochrome P450 3A4 (CYP3A4) inhibitors) Cannabidiol is broken down by the liver. Some medications might decrease how quickly the liver breaks down cannabidiol. Taking cannabidiol along with these medications might increase the effects and side effects of cannabidiol.
Some medications that might decrease how quickly the liver breaks down cannabidiol include amiodarone (Cordarone), clarithromycin (Biaxin), diltiazem (Cardizem), erythromycin (E-mycin, Erythrocin), indinavir (Crixivan), ritonavir (Norvir), saquinavir (Fortovase, Invirase), and many others. Medications that increase breakdown of other medications by the liver (Cytochrome P450 3A4 (CYP3A4) inducers) Cannabidiol is broken down by the liver. Some medications might increase how quickly the liver breaks down cannabidiol. Taking cannabidiol along with these medications might decrease the effects of cannabidiol.
Some of these medicines include carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), rifampin, rifabutin (Mycobutin), and others. Medications that increase the breakdown of other medications by the liver (Cytochrome P450 2C19 (CYP2C19) inducers) Cannabidiol is broken down by the liver. Some medications might increase how quickly the liver breaks down cannabidiol. Taking cannabidiol along with these medications might decrease the effects of cannabidiol.
Some medications that might increase the breakdown of cannabidiol in the liver include carbamazepine (Tegretol), prednisone (Deltasone), and rifampin (Rifadin, Rimactane). Methadone (Dolophine) Methadone is broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down methadone. Taking cannabidiol along with methadone might increase the effects and side effects of methadone. Rufinamide (Banzel) Rufinamide is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down rufinamide. This might increase levels of rufinamide in the body by a small amount. Sedative medications (CNS depressants) Cannabidiol might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking cannabidiol along with sedative medications might cause too much sleepiness.

Some sedative medications include benzodiazepines, pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), thiopental (Pentothal), fentanyl (Duragesic, Sublimaze), morphine, propofol (Diprivan), and others. Sirolimus (Rapamune) Sirolimus is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down sirolimus. This might increase levels of sirolimus in the body. Stiripentol (Diacomit) Stiripentol is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down stiripentol. This might increase levels of stiripentol in the body and increase its side effects. Tacrolimus (Prograf) Tacrolimus is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down tacrolimus. This might increase levels of tacrolimus in the body. Topiramate (Tompamax) Topiramate is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down topiramate. This might increase levels of topiramate in the body by a small amount. Valproate Valproic acid can cause liver injury. Taking cannabidiol with valproic acid might increase the chance of liver injury. Cannabidiol and/or valproic acid might need to be stopped, or the dose might need to be reduced. Warfarin Cannabidiol might increase levels of warfarin, which can increase the risk for bleeding. Cannabidiol and/or warfarin might need to be stopped, or the dose might need to be reduced. Zonisamide Zonisamide is changed and broken down by the body. Cannabidiol might decrease how quickly the body breaks down zonisamide. This might increase levels of zonisamide in the body by a small amount.

Cannabidiol is a chemical in the Cannabis sativa plant, also known as marijuana or hemp. One specific form of CBD is approved as a drug in the U.S. for seizure.

CBD Drug Interactions Explained: What Drugs Should Not Be Taken With CBD

Last update: February 2021

Table of contents:

  • Understanding Metabolism
  • The Cytochrome P450 System
  • CBD and Drug Interactions: Contraindications
  • CBD and Drug Interactions in Studies
  • List of drugs and medications which could be contraindicated for use with CBD
  • Speak to Your Doctor
  • Key Takeaways

Cannabidiol, or CBD, is one of over a 100 different types of a specific kind of compound called phytocannabinoids found in the Cannabis sativa plant.

CBD is has become increasingly popular in recent years due to its wide range of therapeutic effects as well as its ability to relieve a host of symptoms effectively , but also to do so safely and with few side effects. And unlike tetrahydrocannabinol (THC), the other most abundant phytocannabinoid found in the cannabis plant, CBD is non-intoxicating and non-psychoactive – something that for many people is an undesirable yet unavoidable part of taking a high-THC containing cannabis extract.

CBD is most widely known and has been popularized as being used for seizure disorders such as epilepsy, but has also proven to be effective in helping to relieve the symptoms of other conditions. These include anxiety, depression, schizophrenia, inflammatory and neuropathic pain, Parkinson’s disease, Crohn’s and other forms of inflammatory bowel disease, as well as certain types of cancer.

However, despite the fact that the vast majority of the science indicates CBD oil is safe to use on its own, CBD is a powerful compound that interacts with a variety of systems within the body. And as such, CBD not only shows potential as a powerful therapeutic agent, but can become less benign when taken together with other substances such as pharmaceutical drugs.

Let’s find out why.

Understanding Metabolism

Before we take a look at how CBD interacts with medications, first we need to understand how the body’s metabolism works in general, the systems involved in CBD metabolism, how CBD is metabolized and how CBD affects something called the Cytochrome P-450 system.

What Is Metabolism?

A lot of people think of metabolism in terms of how easily or slowly they gain and lose weight, often claiming to have a “fast” or “slow” metabolism. In scientific terms, this is what is known as the basal metabolic rate, or the amount of calories an individual requires in order to sustain normal body functions while at rest.

However, this basal metabolic rate is very different to metabolism – the way in which substances such as different types of food are broken down and used by the body – with much of this process happening in the gut and the liver in what is known as the ‘first-pass effect,’ or ‘first-pass metabolism’.

Explained very simplistically, when food is eaten, it is broken down by the liver into its individual compounds in order for it to be used by the body. So, for example, carbohydrates are broken down into sugars, fats into triglycerides, and proteins into amino acids. From there, the metabolism, under the control of chemicals called enzymes, transforms these compounds into metabolites that can then be used by the body, for instance as fuel for cellular processes or as building blocks for various systems and tissues.

Metabolism of CBD

Just like food has to go through this process, so too does a therapeutic compound such as CBD, but in what is more specifically called drug metabolism. Drug metabolism refers to the rate at which medications and other therapeutic compounds are broken down by the body into its individual metabolites and how long these metabolites stay in the body.

So, when CBD is ingested by mouth, either as an oil, tincture, capsule or edible, it has to pass through the digestive system where it is absorbed into the bloodstream by the intestines. From there, the CBD is transported by the blood to the liver where it enters the liver via the hepatic portal. Once the CBD is in the liver, it is broken down into its metabolites by enzymes, after which it can be circulated throughout the body in the bloodstream.

The Cytochrome P450 System

However, in addition to breaking compounds down into metabolites, is also has one other very specific and important role it plays during this metabolic process – the detoxification and excretion of foreign drugs (called xenobiotics) and other types of toxic substances.

It does through a system called the cytochrome P450 system (CYP) which consists of a special group of enzymes containing heme as a cofactor to convert fat-soluble compounds into more water-soluble compounds and aiding in their absorption and use.

It is estimated that the CYP system is responsible for metabolizing over 60% percent of any drug that has been consumed. And interestingly, pharmaceutical researchers and doctors also use cytochrome P450 system to understand, calculate and predict drug dosages effects as well as its potential side effects.

For instance, if only one therapeutic compound is being processed by the liver, and the system in general is healthy, scientist can use the average amount of time it takes for the drug or medication to be processed through the CYP to calculate accurate dosage information.

However, there are certain substances that have the ability to affect the way in which the CYP system processes compounds such as CBD that cause certain drugs to metabolize faster or slower than what they would normally have done.

CBD And The Cytochrome P450 System

As mentioned, CBD also has the ability to interact directly with the CYP system in the liver. Preclinical research is showing that the way in which CBD does is by binding to the site where the enzyme activity occurs acting as a “competitive inhibitor”, displacing its chemical competitors, and thus preventing the CYP system from metabolizing other compounds.

The extent to which CBD acts as a competitive inhibitor of the cytochrome P450 binding proteins is mainly dependent on how much CBD is ingested, the unique physiology of the individual as well as the type of CBD product used (e.g. CBD isolate vs. full-spectrum CBD extracts). This is due to these factors determining how tightly the CBD molecules bind to the active site of the metabolic enzyme, with increased and tighter bonds resulting in more competitive inhibition.

What this means in plain English is that CBD sort of “outcompetes” other medications when it comes to reaching first place for getting metabolized by the CYP enzymes. This, in essence, means that CBD deactivates the effects of all the other therapeutic compounds that pass through the CYP system.

How successful it is in its competition with other medicines depends on a few factors, but mostly the amount of CBD that enters into the bloodstream. If it’s not very much, it will have very little to no noticeable effect on the CYP activity and the majority of the medicine will be metabolized. On the other hand, if a large dose of CBD is taken, it will bind to a lot more of the site of enzyme activity and leave a lot more of the other medicine to not be metabolized.

Why CBD’s Competitive Inhibitory Effect On The Cytochrome P450 System Is Important

When the CYP system is affected in this way by CBD, it both changes and the way in which certain other drugs are metabolized as well as prevent a lot of the drug to be metabolized. When this happens, it leads to higher levels of other drug compounds to remain in the body at a single time.

At the very least these elevated concentrations can cause unwanted side effects like an increased risk of bleeding or a suppressed immune system, but more worryingly, it can quite easily result in an overdose.

CBD and Drug Interactions: Contraindications

As mentioned, and contrary to popular belief and anecdotal evidence, CBD is not a biologically inert compound. Rather, CBD has a complex pharmacokinetic and pharmacodynamic profile similar to any other medication, and has the potential to interact with other medications and medical conditions.

For instance, any therapeutic compound that is metabolized by the CYP system has the potential of being affected by CBD. One indication that your medicine might be metabolized by the CYP system is if your pharmacist told you not to eat grapefruit, or watercress or use St. John’s Wort or goldenseal supplements. However, this is by no means a solid test and you should always check with your pharmacist of doctor first (more on that later).

This, along with the rise in the popularity of the medical and complimentary use of CBD, researchers are also starting to investigate drug interactions with CBD more directly.

CBD and Drug Interactions in Studies

For instance, the CBD based drug, EPIDIOLEX® approved in the United States for seizures associated with Lennox‐Gastaut and Dravet syndromes, is increasingly either being used as a supplementary treatment, or even replacing the traditionally used anti-epileptic drugs clobazam, and valproate, as well as stiripentol, topiramate, rufinamide, and N‐desmethylclobazam respectively.

CBD and anti-epileptic drugs

This has spurred researchers to investigate whether there are drug–drug interactions (DDIs) and/or adverse drug events (ADEs) between these traditionally used anti-epileptic drugs and CBD. Data showed that, although there were no serious ADEs, deaths, or pregnancies during the trial, most subjects reported some ADEs of mild severity, while 10.4% subjects reported moderate ADEs, and 2.6% subjects reported severe ADEs, with severe events being characterized by popular rashes. Other moderate ADEs included feeling intoxicated, menstrual discomfort or other mild rashes.

Despite these ADEs, the researchers concluded that the effective dose of 750 mg of cannabidiol (approximately 20 mg/kg/day for a 75‐kg adult), was mostly well tolerated when co-administered with clobazam, stiripentol, or valproate and that ADEs only occurred in patients for which there was no dosage titration.

In another study investigating the interactions between CBD and commonly used anti-epileptic drugs, concluded that, although serum levels of the drugs topiramate, rufinamide, and N‐desmethylclobazam were found when use in conjunction with and increased CBD dosages. However, all changes were within the accepted therapeutic range but did underscore the importance of monitoring serum AED levels and LFTs during treatment with CBD.

CBD and anticancer agents

In yet another such study, but with researchers this time looking into the clinical implications and importance of DDIs between anticancer agents and CBD in patients with cancer, the reviewers found that there was limited information available, with most of the data coming from in vitro studies and that the true in vivo implications are not well-known. This lead them to believe that erring on the side of caution is the best option, and that doctors and pharmacists should always consider the possibility of interactions and their consequences whenever they are aware of a patient using CBD products.

Similarly, a study investigating the potential ADEs and DDIs the researchers highlighted that medical CBD users under clinical supervision should be screened for potential DDIs and ADEs between CBD, other pharmacotherapies, and their underlying conditions. They also recommended that an increase in awareness is needed among the lay public who are recreational or consumer CBD users. Similarly, healthcare providers should also be made aware of the potential for DDIs and ADEs with CBD and strategically prescribe and manage patient regimens while also considering patient desires for complementary or alternative therapies.

List of drugs and medications which could be contraindicated for use with CBD

According to the Indiana University Department of Medicine, pharmaceutical drugs and medications which could be contraindicated for use with CBD include:

  • Steroids and corticosteroids for example hydrocortisone, cortisone, prednisone, triamcinolone and dexamethasone
  • HMG CoA reductase inhibitors (statins) for example atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, simvastatin and rosuvastatin
  • Calcium channel blockers for example amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil
  • Antihistamines for example brompheniramine. cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine and loratadine
  • Prokinetics (motility drugs) for example domperidone, metoclopromide, levosulpiride, renzapride and pruclopride
  • HIV antivirals for example abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir alafenamide and disoproxil fumarate as well as zidovudine
  • Immune modulators for example immune globulins, immunosuppressive agents and immunostimulants, for example bacterial and viral vaccines
  • Benzodiazepines for example alprazolam, clobazam, clonazepam, clorazepate, chlordiazepoxide, diazepam, estazolam and lorazepam
  • Antiarrythmics for example amiodarone, flecainide, procainamide, propafenone, quinidine and tocainide
  • Antibiotics for example amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole-trimethoprim, amoxicillin-clavulanate and levofloxacin
  • Anesthetics for example barbiturates, amobarbital, methohexital, thiamylal, etomidate., ketamine and propofol
  • Antipsychotics for example aripiprazole, asenapine, cariprazine, clozapine, lurasidone, olanzapine, quetiapine, risperidone and ziprasidone
  • Antidepressants for example citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine and vilazodone
  • Anticonvulsants / Anti-Seizure Medications for example acetazolamide, carbamazepine, clobazam, clonazepam, ethosuximide, fosphenytoin, gabapentin, lacosamide, lamotrigine, levetiracetam, methsuximide, nitrazepam, oxcarbazepine, paraldehyde, phenobarbital, phenytoin, primidone, topiramate, valproic acid, vigabatrin, felbamate, tiagabine hydrochloride and zonisamide
  • Beta blockers for example acebutolol, atenolol, betaxolol, betaxolol, bisoprolol fumarate, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, propranolol, sotalol and timolol
  • Proton-Pump Inhibitors (PPIs) for example omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole and dexlansoprazole
  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for example aspirin, celecoxib, diclofenac, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, tolmetin
  • Angiotension II Blockers for example azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan and valsartan
  • Oral Hypoglycemic Agents for example sulfonylureas, meglitinides, biguanides, thiazolidinediones, α-Glucosidase inhibitors, DPP-4 inhibitors, SGLT2 inhibitors and cycloset
  • Sulfonylureas for example glynase, micronase, amaryl, diabinese, glucotrol, tolinase and tolbutamide

There are also other medications known as “prodrugs” that first need to be metabolized into its therapeutic compounds as opposed to being a therapeutic compound in and of itself (like most medications). In other words, the inactive compound is ingested, and once in the body, it is processed into its active compound.

If this processing is dependent on the CYP system, then inhibitors can cause an insufficient amount of the active drug compound to be available in the body, which can result in the desired therapeutic effect not being reached.

One such prodrug for example is codeine which is metabolized into morphine. Similarly, lisdexamfetamine under the brand names Vyvanse and Concerta are two other popular ADHD medications which also fall into this category.

Why You Should Always Speak To Your Doctor First

The above mentioned list of drugs that could interact with CBD is by no means exhaustive and does not include all the medications on which CBD may have an interaction with. Similarly, not all the medication categories listed above will necessarily cause and interaction (although if you are taking one of these medications it is recommended to rather err on the side of caution).

For this reason, it is vital that you should consult your doctor or treating physician before using any CBD oil or product. Your doctor is not only able to advise you with regard to a possible CBD-drug interaction, but can also monitor the therapeutic as well as side effects of both the CBD and the medications you are on. Similarly, your doctor can also help you adjust the dosages of both the medication and CBD so you can take both simultaneously but also do so safely.

Key Takeaways

The safety profile of CBD is well established with study after study showing that it is well tolerated and safe to use, while at the same time rarely producing any serious side effects. Similarly, CBD is a compound that has a profound impact on a wide variety of systems within the body, which is what makes it such an effective therapeutic agent for so many conditions. But at the same time it is good to remember that it is also this, that is the reason why it has the potential to interact with other drugs and why CBD should be consumed with care and respect.

CBD shows potential as a powerful therapeutic agent, but can become less benign when taken together with other substances such as pharmaceutical drugs.