CBD & Drug Interactions​: The Science

As interest in Cannabidiol increases, questions around CBD drug interactions naturally also increase. 

When taken together or within a short period of each other, many drugs have the potential to interact. 

Cannabidiol, although a naturally occurring compound, still acts as a drug as soon as it enters the body. 

When we talk about drugs interacting with each other in the body, we mean when the intended effects or side effects are altered by the simultaneous ingestion of another substance (a food, supplement, or beverage can also cause this).

Join us below for a scientific conversation about how Cannabidiol can interact with medications. 

Types of Interactions

There are two different but related classifications of drug interactions – pharmacokinetic and pharmacodynamic. 

Pharmacokinetic interactions refer to how one substance affects the rate at which another is absorbed and transported around the body. 

Additionally, it may also affect the rate at which the drug is metabolized and excreted. 

This type of interaction will result in varying levels of the drug in your body.

Pharmacodynamics relates to the effect of a drug on the body: Two drugs may have similar effects, and when taken together, may heighten or lessen the intended impact of one another.

For example, two drugs that cause sedation when taken together may result in an increased sedative effect. 

Conversely, one may counteract the effect of another, like taking one drug to increase your blood pressure while taking another that may reduce it.

CBD Drug Interactions: Top Line Summary

Currently, there is little tangible evidence referring to interactions between CBD and other compounds due to the limited number of clinical studies. 

On the flip side, several small studies have looked into how CBD is thought to metabolize in the body, which is a helpful proxy.  

So what drugs should not be taken with CBD?

One study looked into interactions between CBD and commonly used antiepileptic drugs, resulting in raised levels of these drugs in the body. Also, finding elevated Liver Function Test markers (LFT), which in some cases can represent liver toxicity or potential damage.

Clobazam is another drug that is used to treat epilepsy and, in some cases, anxiety. 

A small study of 13 children investigated the use of CBD and clobazam in children, revealed that after four weeks of treatment, clobazam levels rose significantly, resulting in increased side effects such as drowsiness, ataxia, and irritability. 

On the more positive side, the study revealed a 50% decrease in seizures amongst 9 (69%) of the patients.

The use of CBD in epilepsy is one of the most documented use cases of cannabidiol. In the US, the FDA approved the medicine Epidiolex in 2018, a highly concentrated form of CBD for use in treatment-resistant epilepsy such as Lennox-Gastaut syndrome or Dravet syndrome. 

There is a limited amount of research that has looked into the effects of CBD and anticoagulants/antiplatelets (drugs that ‘thin’ your blood to reduce blood clotting). Commonly prescribed medicines in this class include aspirin, clopidogrel, warfarin, and apixaban.

Studies indicate that CBD can have similar effects to these drugs, therefore increasing the likelihood of bleeding. 

The Human Body & Metabolism 

Metabolism refers to the way different compounds are broken down and absorbed by the body.

Any substance we consume must first get broken down to become ready for absorption. Much of this crucial process takes place in the gut and the liver. It’s called the first-pass effect or first-pass metabolism.

Even though CBD is a plant-derived compound, it’s also a powerful one. This is because it interacts with different crucial systems in the body.

CBD metabolic processes involve various enzymes and molecular pathways.

Let’s take, for example, how metabolism works when it comes to the food we consume.

Metabolism allows the body to properly use the food we intake. But, first, food has to be broken down into individual compounds. In this sense, carbohydrates are broken down into sugars.

Next, the metabolism works to transform sugars. This process happens thanks to specific enzymes. Thus, enzymes help to turn sugars into metabolites.

Metabolites have a whole array of complex functions. For instance, they can be used as building blocks for different tissues and internal systems. Or they can be used as fuel for various cellular processes.

The way cannabinoids are metabolized is somewhat similar to the way we metabolize food. In the case of CBD metabolization, though, we’re talking about drug metabolism.

To start with, CBD must pass through the digestive system. Afterward, it’s absorbed into the bloodstream. Then it has to be transported to the liver before entering the body’s general bloodstream.

It’s in the liver where cannabinoids get broken down into metabolites. Once broken down into metabolites they can finally circulate throughout the body and be excreted. 

Only a small fraction, about 13-16%, of edibly ingested CBD goes unbroken and is biologically available.

Related Read: CBD Bioavailability

Important Note

Metabolites can have very different properties than the initial drugs.

That’s why CBD can potentially interact with many pharmaceuticals. By doing so, it can affect drug metabolism by speeding  up or slowing  down enzymes that also commonly process most known drugs. 

As a result, it can alter the effects of certain prescription medications and even supplements.

How does this work?

CBD can inhibit the activity of a family of enzymes known as cytochrome P450.

The Cytochrome P450 System & Prescription Medications 

It’s Cytochrome P450 enzymes that contribute to drug metabolism. Ultimately, drugs like CBD can inhibit or induce cytochrome P450 enzymes.

Why does this matter?

The Cytochrome P450 system is a key enzyme group. It metabolizes most of the drugs we consume, including more than 60% of marketed prescription medications.

The available research highlights that this class of enzymes consists of more than 50 enzymes. Yet only 6 of them are in charge of metabolizing 90% of drugs. 

And yes, this includes when we take CBD. 

The Link Between CBD, Medications & Grapefruit Juice

Ever noticed the “grapefruit warnings” on some type of medication? Or maybe your doctor has warned you not to consume grapefruit when prescribing you a certain medication?

Well, that’s because both Cannabidiol and grapefruits have something important in common.

When it comes to CBD and drug interactions, Cannabidiol can have a similar effect to grapefruit juice. That’s according to the available preliminary research.

The thing is, grapefruits contain compounds known as flavonoids and furanocoumarins. When combined with certain enzymes, furanocoumarins and flavonoids can significantly slow them. One of these enzymes is exactly CYP450.

As mentioned above, the CYP450 enzyme serves a crucial function in drug interactions. It breaks down and removes drugs from your system. That’s why with some health conditions, your doctor may warn you to restrain from grapefruits.

Short Takeaway

Similar to grapefruits, CBD can impair how your body metabolizes some drugs. Furthermore, it can raise the serum levels of those medications in your system.

When serum levels are raised, the CBD product you’ve consumed can theoretically create a dangerous elevation of certain medicines. However, recent systematic reviews have found a low risk of these interactions actually being clinically significant.

So, we have plenty of solid reasons why people must always consult with their healthcare providers before they attempt to take CBD.

Your doctor will check on the compatibility between CBD products and other medications you may use to treat certain health conditions. Thus, you can receive reliable information and guidance to establish the best routine. 

CBD Interactions With Prescription Drugs 

The available research on possible interactions with prescription drugs is rather inconclusive at this point. It depends more on the potential side effects of the prescription drug being too high, rather than any toxicity from CBD itself. 

So, as a rule of thumb, you must always consult with your healthcare provider or doctor first and foremost before you take CBD, especially if you’re prescribed medications.

Below is a summary of information from the latest studies regarding specific interactions for medications available both on prescription and over-the-counter. 

CBD And Gabapentin 

Gabapentin is often used to treat neuropathic pain and epilepsy. In addition, medications derived from CBD and Gabapentin are frequently used to offer respite from seizure disorders. 

Italian researcher Emilio Perucca was the first one to provide evidence that CBD can have a beneficial effect on two rare types of epilepsy: Lennox-Gastaut Syndrome and Dravet syndrome.

According to a 2011 study, researchers concluded that Gabapentin is relatively safe from drug interaction. In addition, the study showed that it bypasses the first-pass enzyme interaction, and most of it is excreted via urination.

However, in 2017 researchers found out that CBD could bind with the GABA_A receptors.
By binding with GABA_A receptors, it can slow down the firing frequency of neurons.

Meanwhile, Gabapentin is a structural analog of gamma-aminobutyric acid (GABA). So, potential interactions between CBD and gabapentin can lead to unwanted effects due to this relationship.

Potential side effects of such an interaction include:

• difficulty concentrating, 
• drowsiness,
• confusion,
• dizziness

CBD And Antidepressants

Zoloft is one example of a common selective serotonin uptake inhibitor (SSRI). 

Serotonin is the “feel-good” hormone and vital neurotransmitter. When its levels decrease, people can feel depressed and have mood swings.

of such interaction include:

• impairment in judgment and motor coordination, 
• changes in thoughts and mood, possibly warranting emergency medical attention
• drowsiness, 
• dizziness, 
• difficulty concentrating.

CBD Oil And Antibiotics 

At this point, there is very little data on the relationship between antibiotics and CBD.

Yet, there is an associated risk when taking CBD and antibiotics together. That’s because the cytochrome P450 enzyme system breaks both down. 

When it comes to science, there are two notable pieces of research:

In a first-of-its-kind study led by the University of Westminster, CBD was found to increase the effectiveness of certain antibiotics.

This was further confirmed by another study led by researchers from the University of Southern Denmark. Although, this increased effectiveness was shown to only work on specific types of bacteria. 

CBD Oil And Vyvanse 

Vyvanse is a pro-drug. A prodrug refers to a medication or a compound that turns into a pharmacologically active drug. It becomes active only after being absorbed and then metabolized in the body.

The same enzyme metabolizes Vyvanse as CBD (the P-450 enzyme). Thus, combining CBD and Vyvanse could lead to unforeseen, increased side effects.

While there are no formal studies on interactions between CBD and Vyvanse, anecdotal reports are growing.

Nonetheless, consult your physician to discuss how Vyvanse may interact with CBD. 

CBD Oil And Tramadol 

According to a 2020 study, CBD could improve sleep and chronic pain among patients who use opioids like Tramadol to manage pain.

However, another study conducted by the American Society for Pharmacology and Experimental Therapeutics concludes that CBD may slow the metabolization of Tramadol.

That’s because CBD use may relate to inhibiting the liver enzyme CYP2DC responsible for the breakdown of tramadol and other over-the-counter medications.

Moreover, high doses of CBD were shown to lessen the analgesic effectiveness of Tramadol despite the fact CBD actually may raise the levels of opioids including codeine and oxycodone. Such CBD and opioid interactions could potentially cause more sedation and be dangerous.

Ultimately, there aren’t enough studies available on the specific drug interaction between CBD and Tramadol. 

Reach out to your qualified health provider for advice. 

CBD And Ibuprofen 

Ibuprofen is one of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Similar to CBD, it is used in the treatment of pain and inflammation.

A study published in the Journal of Neurology Research highlights there have been no reported interactions between CBD and ibuprofen.

But health experts further suggest that potential interactions may be dosage-dependent, leading to unforeseen side effects. 

CBD And Prednisone 

Corticosteroids like hydrocortisone and prednisolone should be cautiously taken with CBD.

This is because CBD and corticosteroids are inhibitors of the CYP450 enzyme system. 

According to the District of Columbia Department of Health, this can increase the risk of systemic side effects. This is due to decreased glucocorticoid clearance. 

CBD Oil And Lamictal Medication

Like other anti-epileptic (AED) medications, Lamictal use often comes accompanied by unwanted side effects.

More people are starting to become interested in CBD as a less debilitating option.

Moreover, a 2019 clinical trial highlights no significant drug-drug effects on treatment response in patients with treatment-resistant epilepsy. However, in general, other research suggests that caution should be used and your doctor may need to monitor liver enzymes (LFTs) if you are on AEDs.

Additionally, studies show that CBD may inhibit an enzyme known as UGT2B7. 

This enzyme is necessary for the metabolization of Lamictal. So, the combination of CBD and Lamictal may increase both of their levels and the risk of aggravation of Lamictal-related side effects.

CBD And Omeprazole 

Omeprazole is a proton pump inhibitor. CBD can inhibit the enzymes that are targeted by Proton Pump Inhibitors (PPIs).

One of the most common side effects is the risk of diarrhea.

Drugs That Should Not Be Taken With CBD

According to recently reviewed science, certain medications should be taken with caution if concomitantly taking cannabinoids like THC and CBD. 

Taking such medications along with cannabinoids must be closely monitored by qualified healthcare providers. These include but are not limited to:

• Amiodarone (heart rhythm medication)
• Levothyroxine (thyroid medication)
• Warfarin (common blood thinner)
• Lamotrigine, Valproate, Clobazam (seizure medications)

Other drugs that relate to adverse reactions concerning CBD use include:

• Oral hypoglycemic agents,
• Prokinetic steroids,
• Immune modulators,
• Calcium channel blockers,
• Valproic acid.

Patients must be especially careful when combining CBD with any OTC or prescription medications that cause sleepiness (such as opioids or antipsychotics, among others). You should never stop taking nor alter prescription medications unless directed by your provider.

Poor Regulation Plays A Part

Research warns us about the potential risks related to drug interactions between marijuana- or hemp-derived products and certain medications.

One of the hidden dangers of such interactions relates to the still poorly regulated CBD market. Many CBD products are mislabeled or improperly checked for purity and cannabinoid concentration. This can increase the risks of unforeseen side effects.

Furthermore, researchers highlight older adults are more susceptible to drug interactions as they are generally (but not necessarily) more likely to be on greater numbers of prescription medications, have more dry weight, and slower metabolisms.

Wrapping Up: CBD & Drug Interactions

Ultimately, some patients should not take CBD.

This is especially true for persons with cardiovascular disease, certrain pulmonary disease, renal disease, severe psychiatric disease, or other critical illness.

With certain medications, the CBD treatment has to be monitored closely by a qualified doctor.

All in all, if you’re taking medication and using cannabis in any form, including CBD, you should always consult your doctor for advice regarding potential undesired consequences and appropriate personalized guidance.