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

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.

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 the 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 causes 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 v.s 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 “out competes” other medications when it comes to reaching first place in 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

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).

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 of the medications on which CBD may have an interaction with. Similarly, not all of 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.

Drugs that May Interact with CBD Oil

Drugs that May Interact with CBD Oil

CBD oil interacts with certain prescription medications, which is why you should always consult your doctor before using cannabidiol.

CBD Oil Drug Interactions – The CYP450 Pathway

Research has begun to demonstrate that cannabidiol (CBD) has the potential to effectively help a large number of people. CBD oil interacts with the endocannabinoid system in a way that produces very few unintended side-effects.

While the majority of the vast majority of the science indicates CBD oil is safe for use and consumption, it does pose a few risks that, if not properly understood, could be dangerous.

One of these risks is the inhibition of the cytochrome P450 enzyme system .

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What is the Cytochrome P-450 System?

Found within the liver, the cytochrome P450 enzyme system is responsible for metabolizing potentially toxic compounds, including over 60% percent of any drugs you have consumed.

According to Davis’s Drug Guide, this system contains more than 50 enzymes that process and eliminate toxins.

Why Does CYP450 Matter?

In order to determine the appropriate dosages of medications, doctors make calculations using the average amount of time it takes for various drugs and medications to be processed through the cytochrome P450 system.

If only one drug is being processed, and the system is generally healthy, these averages provide accurate dosage information.

However, certain substances have the ability to affect processing times within this system, making drugs metabolize faster or slower than they would on their own.

Similarly, if the cytochrome P450 system is unhealthy due to problems with the liver or other pre-existing conditions, drugs may not metabolize as they should.

Cannabidiol in the Cytochrome P-450 System

Cannabidiol can inhibit the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times.

Interestingly, CBD oil is not alone in its effect on drug metabolism. Grapefruit , watercress , St. John’s Wort , and goldenseal all have a similar impact in terms of CYP450 inhibition.

When the CYP450 system is impacted in this way, it leads to higher levels of certain drugs in your system at one time. This can cause unwanted side effects, and sometimes, an overdose.

If you are taking a medication affected by cannabidiol, you should consult your doctor to make sure that it is safe for you to supplement your personal care routine with CBD oil. From there, the two of you may consider adjusting the dosage on your medications so that you can use both products safely.

Drugs that Interact with Cannabidiol

Any drug metabolized by CYP450 enzymes could potentially interact with cannabidiol. According to the Indiana University Department of Medicine , drugs known to use the CYP450 system include:

  • Steroids
  • HMG CoA reductase inhibitors
  • Calcium channel blockers
  • Antihistamines
  • Prokinetics
  • HIV antivirals
  • Immune modulators
  • Benzodiazepines
  • Antiarrythmics
  • Antibiotics
  • Anesthetics
  • Antipsychotics
  • Antidepressants
  • Anti-epileptics
  • Beta blockers
  • PPIs
  • NSAIDs
  • Angiotension II blockers
  • Oral hypoglycemic agents
  • Sulfonylureas

This list does not include all of the potential medications impacted by cannabidiol. Nor will every medication in the categories contained on this list will cause an interaction. For these reasons, you should consult with a medical professional before supplementing with CBD oil.

There are certain medications, known as “prodrugs,” that need to be metabolized to produce the therapeutic compound. In other words, you ingest an inactive compound and once in the body, it is processed into the active drug. If this processing is dependent on CYP3A4 (part of the larger CYP450 system), then inhibitors can result in too little active drug in the body for the desired therapeutic effect.

Codeine , for example, is a prodrug that is metabolized into morphine which provides the effect.

Vyvanse and Concerta are two other popular pharmaceutical medications for ADHD that fall into this category.

If you are worried that your CYP450 pathway may not be functioning properly, physicians can test the system to ensure that the medications you take are metabolizing as expected.

Combining Alcohol and CBD Oil

Alcohol and cannabis are both widely consumed in our society and the effects of combining the two are well known.

What is less understood by the general public, is the effects of combining alcohol and the cannabinoid compound CBD.

Alcohol depends on a few different metabolic pathways in the human body, with the primary enzymes involved being:

In people who only drink socially or occasionally, ADH and ALDH handle the entire workload of metabolizing ethanol. However, when binge drinking (or during chronic consumption of alcohol) CYP450 gets involved to assist the overloaded ADH and ALDH pathways.

Here are some interesting tidbits about alcohol and CBD oil:

  • The CB1 receptor is a significant player in the reinforcing and motivating attributes of alcohol. [ S ]
  • Combining alcohol and CBD results in significantly lower blood levels of alcohol. [ S ]
  • CBD reduces the reinforcement, motivation and relapse for alcohol. [ S ]
  • CBD protects the liver from damage done by binge-drinking alcohol. [ S ]
  • CBD prevents against alcohol-induced neurodegeneration. [ S ]
  • CBD attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury. [ S ]
  • Cannabinoids have an effect on nearly all enzymes responsible for metabolizing alcohol. [ S ]
  • CB1 receptor agonists (THC) encourage alcohol consumption, while CB1 receptor antagonists (CBD) decrease it. [ S ]

Although the pharmacokinetics of alcohol and CBD are not yet well-understood, what we do know is CBD inhibits the CYP450 enzyme system, and this system plays a significant role in alcohol metabolism.

Additionally, as found in mice, CBD alters levels of ADH and ALDH to varying degrees.

It is important to be mindful and cautious when mixing CBD and alcohol.

Caffeine and CBD – Better than a PB&J

Caffeine is the world’s most famous and commonly consumed psychoactive drug. Who doesn’t ingest even a little from time to time?

CBD oil is rapidly gaining ground on coffee in terms of popularity and so it only makes sense that people would start combining the two.

As it turns out, the two substances go very well together!

Caffeine is molecularly very similar to adenosine , a compound produced in our bodies that activates the A2a receptor. Caffeine binds to the A2a receptors, inhibiting the reuptake of adenosine.

When adenosine binds to the A2a receptor, the result is what is commonly known as the ‘ rest and digest ’ effect. Consequently, blocking adenosine from binding results in vasodilation , which increases clarity and alertness.

CBD oil is also a partial agonist of the A2a receptor; so the theory goes that by combining caffeine and CBD, adenosine is blocked across the board, resulting in not only more stimulation, but reduced anxiety (due to CBD’s effects on other neurotransmitters systems).

It is worth noting that these effects depend on the serving size of the CBD. High amounts of CBD are more likely to cause drowsiness and sedation.

Additionally, caffeine is metabolized by a CYP450 enzyme, specifically CYP1A2 . As CBD inhibits the CYP450 enzyme system, a slowed excretion rate of caffeine will occur. This can mean the effects of the caffeine will be more prolonged and drawn out. The can be both good and bad!

On the bright side, CBD oil and caffeine together will cause the boost from your morning cup of coffee to last all day instead of just a few hours. On the downside, it’s easy to overdo it and end up wide-eyed in bed when you are trying to go to sleep.

Considering this information, again, it is best to be mindful and cautious when mixing caffeine and CBD.

Can CBD Oil Be Addictive?

One of the most common questions we get is: Can I get addicted to CBD oil? The answer depends on what you mean by “addicted.”

When looking at the chemical impacts of CBD oil, the answer is no. Cannabidiol is not physically addictive in the same way opiates, cocaine, alcohol, and other drugs can be. Also, CBD oil does not produce any physical withdrawal symptoms when you stop using it. In fact, CBD oil is currently being researched as a potential tool for minimizing the severe withdrawal from drugs like opiates.

But, having said that, human beings can get addicted to just about anything including exercise, music, sex, and food.

Because CBD oil can alter essential liver enzymes , it is crucial to do your research, talk to your physician, and figure out how to best consume CBD oil for your specific situation.

Information and education will be your most powerful weapons going forward.

How To Use CBD Oil

When taking cannabidiol, it is important to consume only the recommended serving size.

Raising or lowering this amount may produce the opposite of the desired effect.

Keep in mind that some people may metabolize cannabidiol differently because of anomalies within the cytochrome P45O (CYP450) enzyme system. And depending on when you take your medications, you may find an unintended increase or decrease in CBD concentrations in your blood.

If you suspect that you are not metabolizing CBD oil as expected, ask your doctor to test your cytochrome P450 enzyme system before adjusting your dosage.

Also, you may refer to our page on dosing CBD oil for additional information.

Some of CBD oil's side effects can be dangerous if you do not understand the Cytochrome P-450 System. Discover which drugs are dangerous to combine with CBD. ]]>