Does CBD Gummies Interact With Medications

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Studies have shown CBD to be a safe substance, but you should be mindful of possible CBD drug interactions if you are taking other medications. CBD is broken down by the same enzyme as 75% of medications and drugs. Here is a list of the medications that interact with CBD and if it's safe to mix.

A Patient’s Guide to CBD and Drug Interactions

Does CBD interact with medications? Studies have shown CBD to be a safe substance, but as with any new drug, you must make sure it doesn’t negatively interact with your medications.

CBD drug interactions vary on the type of medication you are taking, so discussing CBD use with your doctor is crucial before starting a CBD regimen.

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Cannabidiol (CBD) is a well-known component of hemp with diverse health benefits such as reducing pain and inflammation after physical activity, relief from occasional sleeplessness, as well as improvements in focus, mood and resilience to stress.

Numerous studies have shown that CBD is a safe, non-impairing, and non-habit-forming substance. The safety profile of CBD has been acknowledged by major health agencies, such as the World Health Organization (WHO), showing that it’s well-tolerated by animals and humans and rarely produces any dangerous side effects.

Jump to: Blood Thinners | Seizure Medications | Statins | Antibiotics | Antidepressants | Immunosuppressants

However, while CBD is safe to take with many medications, it has the potential to produce problematic interactions with others. Most often, CBD interacts with other drugs via liver metabolism.

In this article I’ll explain how and why these interactions occur and describe the classes of medications that are processed by the same liver enzymes the body uses to process CBD.

The key takeaways for you to remember are:

  • CBD is unlikely to cause drug interactions at low and moderate doses used by most consumers of artisanal products. Drug interactions reported in the scientific literature most often occur at very high doses used in clinical trials of epilepsy and other conditions.[1]
  • The most important drug interactions can be predicted by comparing the CYP450 metabolic pathways used by CBD and other drugs.
  • You can help educate your medical providers on drug interactions and other aspects of CBD and medical cannabis by using the information you’ve learned from this article and our cannabis education site to ask informed questions.

How Do CBD Drug Interactions Occur?

There are two main types of drug interactions: those that change the absorption, metabolism, and excretion of one or both drugs (pharmacokinetic interactions), and those based on the mechanism of action of the drugs (pharmacodynamic interactions). Since cannabinoids, including CBD, share metabolic pathways with other drugs, and have similar mechanisms of action with other drugs, the potential for interaction exists. Most of the clinically relevant interactions of CBD with other drugs are related to competition in the liver’s detoxification pathways. Sometimes the combination can make each substance stronger, by slowing metabolism and increasing the levels of the drugs in the body, or one can weaken the effects of the other by speeding up its metabolism. Either can lead to unintended side effects.

Of the 50+ liver enzymes that make up the CYP450 family of drug-metabolising enzymes, two are primarily responsible for metabolizing CBD: CYP3A4 and CYP2C19. Knowing these can allow you or your healthcare provider to look up the metabolism of a pharmaceutical drug and determine if a CBD-drug interaction is possible.

Most of the documented CBD-drug interactions in humans, as well as in rodent studies, have resulted from high doses of CBD that are not typical of most users, but may be used under medical supervision in the treatment of seizures or other serious conditions.

In general, most of the potential drug interactions are theoretical and unlikely to occur in most CBD users. Based on my clinical experience, it is rare for people to experience CBD-drug interactions at doses below 100mg daily. [2]

Most Common CBD Drug Interactions

CBD and Warfarin and other blood thinners

I’m most often asked about interactions that can occur with the blood thinner warfarin (also known as by the brand names Coumadin® and Jantoven®). The more accurate concern with warfarin is its interaction with THC because both warfarin and THC are metabolized by the liver enzyme CYP2C9. When warfarin and THC compete for processing by this enzyme, warfarin levels can increase and thereby increase the risk of bleeding. Patients using warfarin need to have their blood INR level tested after adding THC-containing cannabis to their regimen.

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While it is possible that taking large amounts of CBD with warfarin or other blood thinners can cause a harmful interaction, the risk is less concerning because the enzyme that metabolizes CBD (CYP2C19) is different. One case report, however, was published demonstrating the need to adjust warfarin dosage after starting and titrating CBD to a very high dose. [3]

Based on this one report, individuals using high doses of CBD concurrently with warfarin should also notify their medical provider and have their blood INR tested. In my clinic, I have never seen any changes in INR when my patients add CBD.

There is also a theoretical interaction between CBD and the direct-acting oral anticoagulants like apixaban and rivaroxaban, based on the CYP3A enzyme (and P-gp efflux transporter), potentially increasing the risk of bleeding. While no cases of interactions between CBD and these drugs have been reported in the scientific literature, people using these drugs and high doses of CBD should monitor for signs of easy bruising and bleeding. [4]

Finally, the antiplatelet drug clopidogrel is metabolized into its active metabolite by CYP2C19, and to a lesser extent, CYP3A4. Therefore, taking CBD with clopidogrel could result in decreased therapeutic effects of the clopidogrel, and clinicians may choose to monitor for appropriate platelet response and aggregation. Again, this interaction is theoretical, with no case reports in the scientific literature. [5]

CBD and Seizure Disorder Medications

Drug interactions with CBD are most common in patients with seizures, especially those using high doses of CBD. When administered with CBD, the blood levels of the following drugs may increase: [6]

  • topiramate
  • rufinamide
  • n-des-methylclobazam (an active metabolite of the drug clobazam)
  • zonisamide
  • eslicarbazepine

Patients combining CBD with the seizure drug valproic acid should monitor liver function for potential abnormalities.

CBD and Statin Cholesterol Medications

Statins are a common family of drugs to consider for interaction with CBD because most are processed by the CYP3A4 enzyme. Taking CBD with statins can theoretically raise the levels of statins in the body, increasing the risk of side effects. Additionally, statins are less compatible with CBD because statins tend to cause side effects that are common and similar to the symptoms we tend to treat with CBD. For example, most statin drugs can cause memory issues, muscle pain, fatigue and muscle weakness.

Because I treat a large number of patients with chronic pain, who are already are taking the maximum allowed daily dose of their statin, I frequently discuss alternatives with their prescriber, including switching to pravastatin, a statin that is metabolized by other routes, reducing the amount of the current statin, or adding coenzyme Q10 to mitigate potential statin-related adverse effects.

CBD and Erythromycin and Azole Antifungals

The antibiotic erythromycin and the azole family of antifungals are common medications that inhibit CYP enzymes that metabolize CBD. Taking them together could theoretically increase the risk of adverse effects.

CBD and Antidepressant Drugs

Several antidepressant and antipsychotic drugs are metabolized by the same enzymes as CBD, and taking them in combination could theoretically increase the likelihood of adverse effects. In six patients on citalopram or escitalopram, the addition of CBD (200 – 800 mg daily) significantly increased citalopram blood concentrations. Adverse events reported for these participants were mild and included fatigue, diarrhea, and nausea. [7]

Furthermore, like many antidepressants, CBD stimulates serotonin receptors, and taking more than one drug with this mechanism of action could theoretically increase the risk of a rare condition called serotonin syndrome. No case reports of this interaction have been described in the scientific literature.

CBD and Immunosuppressant Medications

CBD has the potential to affect the metabolism of the immunosuppressant drugs cyclosporine and tacrolimus via liver metabolism, which may result in increased blood levels of these drugs and an increase in the potential toxic side effects. [8]

CBD and Glaucoma

Glaucoma is still the first condition many people think of when they consider cannabis as a medicine. The evidence is clear that THC can reduce elevated intraocular (eye) pressure (IOP), a hallmark of the condition.

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Does CBD also help? While the answer is not entirely straightforward, the evidence suggests that it does not, and may actually cause harm.

  • A recent animal study found that, unlike THC, CBD actually raised intraocular pressure. The researchers determined the pressure elevation was caused by the effects of CBD on the CB1 receptor (negative allosteric modulation). The same study found that adding CBD to THC completely blocked the IOP-lowering effects of the THC. [9]
  • One human study on patients with elevated IOP found that 20 mg of CBD had no effect, but 40mg caused a slight increase in IOP. [10]

Unlike CBD, CBDA is not likely to have any impact on IOP since it does not share CBD’s activity on the CB1 receptor.

If you have glaucoma and start using CBD products, I recommend having your eye pressures checked to determine if the CBD is causing elevated pressure.

People with glaucoma wishing to use cannabis to lower their IOP will likely do best with THC-dominant, low-CBD preparations. People with glaucoma who wish to use hemp products to address other symptoms will likely do best with CBDA formulas.

People with glaucoma who have well-controlled IOPs wishing to use cannabis to protect the retina are most likely to benefit from a combination of CBD and THC.

Talk with Your Doctor Before CBD Use

If you take several different medicines, see more than one doctor, or have certain health conditions, you and your doctors need to be aware of all the medicines you take to avoid potential drug interactions.

A consultation with a doctor experienced in CBD and cannabis use can help you establish the right routine for your medications and supplements to avoid potentially negative interactions. Some compounds work synergistically with CBD, so asking your doctor can help you maximize the effect of your treatment.

Use online drug interaction checkers to see which cytochrome p450 enzymes are used. If they overlap with CBD (You may have to enter “Epidiolex” if it does not recognize cannabidiol), then monitor more closely and be sure to tell your medical provider. The need for caution increases with higher doses. Using small amounts poses a very low risk of drug interactions.

References

[1] Stout, Stephen M., and Nina M. Cimino. “Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.” Drug metabolism reviews 46.1 (2014): 86-95.
[2] Alsherbiny, Muhammad, and Chun Li. “Medicinal Cannabis—Potential Drug Interactions.” Medicines 6.1 (2019): 3.
[3] Grayson, Leslie, et al. “An interaction between warfarin and cannabidiol, a case report.” Epilepsy & behavior case reports 9 (2018): 10.
[4] Paduch, McKenzie, and Angela R. Thomason. “Potential Drug Interactions Between Cannabinoids and Its Derivatives and Oral Anticoagulants.” Hospital Pharmacy (2021): 0018578720985438.
[5] Greger, Jessica, et al. “A review of cannabis and interactions with anticoagulant and antiplatelet agents.” The Journal of Clinical Pharmacology 60.4 (2020): 432-438.
[6] Gaston, Tyler E., et al. “Interactions between cannabidiol and commonly used antiepileptic drugs.” Epilepsia 58.9 (2017): 1586-1592.
[7] Anderson, Lyndsey L., et al. “Citalopram and cannabidiol: in vitro and in vivo evidence of pharmacokinetic interactions relevant to the treatment of anxiety disorders in young people.” Journal of clinical psychopharmacology 41.5 (2021): 525-533.
[8] Balachandran, Premalatha, Mahmoud Elsohly, and Kevin P. Hill. “Cannabidiol interactions with medications, illicit substances, and alcohol: A comprehensive review.” Journal of general internal medicine (2021): 1-11.
[9] Miller, Sally, et al. “Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.” Investigative ophthalmology & visual science 59.15 (2018): 5904-5911.
[10] Tomida, Ileana, et al. “Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study.” Journal of glaucoma 15.5 (2006): 349-353.

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Dustin Sulak, DO

Dustin Sulak, DO, one of the first physicians in Maine to incorporate the legal use of cannabis as a medicine in 2009, is the founder of Integr8 Health, a medical … Read More

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CBD Drug Interaction List: Is it Safe to take CBD with your Medications?

CBD is phenomenally popular right now. It’s being used to treat pain, anxiety, epilepsy, psychosis, and even neurodegenerative diseases like Alzheimer’s and Parkinson’s. It’s been called a “wonder drug,” without irony, and it has essentially no known downsides. It is readily available and easy to take.

At the same time, it’s important to be aware that CBD can interact with some medications. Taking it at the same time as other drugs can affect CBD’s dosage and effects, and can even change how your body breaks it down.

This article is your guide to safely taking CBD alongside your other medications and supplements. First, it has a quick overview of how CBD interacts with other drugs in your body, and then it lists the most common drugs that interact with CBD, and which you should be careful about taking at the same time. If you want to skip ahead, you can find the list here.

The CYP450 Pathway

Once a drug enters your system, its molecules are circulated through your blood and interact with your cells and tissues, doing whatever it is they’re supposed to do. Painkillers reduce pain signals and can stop swelling, antidepressants interact with brain cells to change your brain chemistry, and so on.

Once they’ve done their work, your body needs to get rid of the drug molecules. Too much of any drug in your bloodstream is toxic, and can start to harm your body.

Your body uses all kinds of systems to get rid of drugs, and the most important of these are enzymes–chemicals that break down other chemicals. The largest set of enzymes are the cytochrome p-450 group (or CYP450), which are responsible for breaking down about 75% of the medications and recreational drugs that we take.

CBD and the CYP450 Pathway

CBD interacts with the CYP450 system in three ways. First, some of the enzymes in the system are responsible for breaking down CBD molecules, as they are for molecules of other drugs. That’s normal–nothing to worry about there.

Second, CBD can affect how CYP450 enzymes are produced by your liver, making it produce not enough of some enzymes or too much of others. This can stop your liver from processing some drugs, like the epilepsy medications clobazam and valproic acid.

Third, and most importantly, CBD can actually stop many of the CYP system’s enzymes from working properly. This is called “inhibition,” and it can cause problems if it prevents the enzymes from breaking down other drugs. Sometimes, the enzymes are responsible for activating other drugs instead, but the same problem comes up–if CBD stops the enzyme from working, then it doesn’t do its normal job, and the other drug won’t behave normally, which can have negative consequences.

For instance, there’s a group of antidepressants called selective-serotonin reuptake inhibitors, which include drugs like citalopram, norfluoxetine, and sertraline. Normally, an enzyme called CYP3A4 breaks down molecules of those drugs, making sure they don’t build up to unsafe levels that can damage cells or tissues. CBD inhibits CYP3A4, though, which means that taking CBD and sertraline at the same time could be dangerous. CYP3A4 wouldn’t break the sertraline down, and it would accumulate for far too long.

It’s worth noting that CBD isn’t the only thing that does this. The herbs St. John’s Wort and goldenseal can also stop CYP450 enzymes from working properly, as can grapefruit and starfruit juice, and even tobacco.

Drugs that Interact with CBD List

That brings us to our list. Remember, the general rule is that you need to be careful taking CBD at the same time as any drug or medication that gets processed by CYP450 enzymes. If you’re thinking about doing so, be sure to check with your doctor first.

Here are the most common of those drugs and medications. They include many painkillers, anti-inflammatories, antipsychotics, antidepressants, anticonvulsants, statins, opioids, and other groups.

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