What Not To Mix With CBD

Although cannabidiol (CBD) grows more popular with each passing year, there is not nearly enough talk regarding potential CBD drug interactions. While an effective solution for many illnesses, using this non-psychoactive substance can lead to unpleasant side effects — especially when taken with other medications.

Like medical cannabis, CBD may interact with certain drugs, leading to severe health issues. As such, you should learn more about its drug profile and how it may alter the effects of other drugs before using a CBD product.

Whether you use over-the-counter medications, herbal remedies, or prescription drugs — knowing how CBD interacts with other compounds might very well save your life. Read on to find out what drugs should not be taken with CBD and how it can affect your drug metabolism.

What Drugs Should Not Be Taken With CBD?

In 2020, researchers from Penn State College of Medicine created a list of delta-9-THC and CBD drug-drug interactions. During the research, they focused on five cannabinoid medications: Epidiolex, Sativex, Marinol, Syndros, and Cesamet.

The list features 57 prescription medications, with notable inclusions of numerous heart medications and antibiotics. While not all of these interact negatively with CBD products, some of those that do are commonly used by millions of people every year. Taking a look at this list is an excellent first step in determining whether the drug you want to take is safe to use with CBD.

Here are a few examples of narrow therapeutic index (NTI) drugs features on the list that may potentially result in drug interactions with CBD.

Amiodarone

Amiodarone is a heart rhythm medication only prescribed in severe cases of ventricular arrhythmias. The reason for it is straightforward — the high risk involved with using it. The most common side effects of amiodarone are nausea, vomiting, fatigue, and constipation.

Most importantly, researchers have associated this substance with multiple systemic adverse effects, including liver function derangements, hypothyroidism or hyperthyroidism, ocular deposits, pulmonary toxicity, and bradycardia.

While amiodarone can produce serious side effects on its own, CBD can increase its concentration to potentially life-threatening levels.

As an anti-arrhythmic medication, amiodarone needs to be precisely dosed. Otherwise, the patient may experience unwanted side effects, or the drug’s effectiveness can be decreased. It is metabolized by liver enzymes — mostly CYP3A4 and CYP2C8. As CBD may inhibit CYP2C8, it might alter concentrations of amiodarone in the body.

Clobazam

Clobazam — a standard treatment for Dravet Syndrome — may work exceptionally well in tandem with CBD. The latest research suggests that combining these two drugs results in a more substantial anti-seizure effect than either treatment alone.

With this being said, it might be wise to only opt for one of these medications for the time being, as this interaction is yet to be thoroughly tested on humans.

Lamotrigine

Lamotrigine is a medication used to treat epilepsy. CBD oil may boost its levels by inhibiting glucuronidation (UGTs) or downregulating efflux transporters. As a result, it can increase the risk of skin reactions — a common side effect of lamotrigine.

Other side effects that may occur after lamotrigine use include changes in vision, chest pain, irregular heartbeat, and poor coordination.

Levothyroxine

Levothyroxine is a thyroid medication frequently used to treat hypothyroidism, including Hashimoto’s disease and myxedema coma. In 2019, it was the second most commonly prescribed medication in the United States, with over 102 million prescriptions. As many people take CBD to deal with inflammation caused by hypothyroidism, it may raise concerns about potential adverse interactions between CBD-only products and levothyroxine.

Currently, we know that both of these drugs compete for metabolism, as they require the same pathway to metabolize — cytochrome P450. Because of this interaction, CBD may cause more thyroxine to be compiled, potentially leading to hyperthyroidism. Other side effects of using levothyroxine with CBD include mild nausea and anxiety.

Valproate

Valproate, often prescribed in the form of valproic acid or sodium valproate, is a common antiepileptic drug. It is primarily used to treat epilepsy and bipolar disorder. Nonetheless, it is also frequently taken to prevent migraine headaches.

When used with CBD, its levels may increase, potentially resulting in hepatic damage. Individuals should consult their healthcare providers before taking these medicines together.

Warfarin

People with a medical condition like valvular heart disease often use multiple medications to reduce the risk of having a stroke. One of these is warfarin — a blood thinner used to prevent blood clots. Overall, it is the most commonly used oral anticoagulant worldwide.

The problem with using CBD and warfarin is that they are both metabolized by the cytochrome P450 enzyme system. Consequently, taking these substances together may alter warfarin’s activity. For example, it can increase warfarin plasma concentrations, potentially increasing the risk of bleeding.

Other Potential CBD Drug Interactions

Even though Epidiolex is the only CBD-based drug approved by the Food and Drug Administration (FDA), many people turn to other hemp-derived CBD products to alleviate their health conditions. The potential health benefits of CBD include pain relief, decreased blood pressure, and reduced symptoms of seizure disorders.

However, as cannabidiol is not a biologically inert compound, using CBD oil may compromise the metabolism of certain medications and pharmaceutical drugs. Due to CBD interaction, immune modulators, drugs affecting blood pressure, calcium channel blockers, and many other therapeutic compounds may become less effective.

Here are some commonly used drugs that, when taken with CBD, may result in an increased risk of side effects.

Ibuprofen

Ibuprofen belongs to the group of Non-Steroidal Anti-Inflammatory Drugs (NSAID). As such, it possesses the same anti-inflammatory properties as CBD oil. But, drugs from this group are also known to interact with cannabinoids present in the cannabis plant — including CBD.

If taken simultaneously, ibuprofen and CBD may lead to unforeseen consequences, including severe damage to the nervous system. As a result, it is best to stick to only one of these therapeutic compounds.

Lamictal

Depending on the dosage, lamictal and CBD can induce numerous side effects. These include but are not limited to:

• dizziness,
• confusion,
• drowsiness,
• impairment in judgment, thinking, and psychomotor skills,
• difficulty concentrating.

As there is still a lot to uncover about interactions between CBD and lamictal, it is best to avoid using these substances simultaneously.

Omeprazole

If you use omeprazole or other Proton Pump Inhibitors (PPIs), taking CBD is not advisable. As the same enzymes process both these substances, their side effects may become significantly enhanced or hampered. These may include dryness of the mouth, drowsiness, and headache. Furthermore, taking CBD with heartburn medications could increase the risk of diarrhea.

Prednisone

Prednisone is a glucocorticoid medication, meaning it interacts with the CYP450 enzyme system. CBD inhibits some enzymes in this system, leading to possible interactions between these two drugs.

CBD can enhance common side effects of prednisone, such as headache, changes in mood, extreme tiredness, and dizziness. Because of this, you should never take corticosteroids like prednisone and CBD together.

What Is Drug Metabolism?

The term “metabolism” refers to the basal metabolic rate — the way your body uses energy for weight management. It is used to describe all chemical reactions involved in sustaining the living state of the organism.

On the other hand, drug metabolism refers to the process of breaking compounds by the organism. This process mainly occurs in the liver, where carbohydrates are broken down into sugars, proteins into amino acids, and fats into triglycerides.

Drugs, like other substances, are also broken down in your liver. After this process, they are “guided” by specific enzymatic systems and transformed into their individual metabolites, which affect various processes in your body. After they are used up, they are flushed with urine.

How Does CBD Affect Drug Metabolism?

CBD binds to the active site of the metabolic enzyme, potentially increasing the amount of time other medications are in the system. This process is known as competitive inhibition, and it can prolong or increase the likelihood of unwanted side effects, such as decreased appetite and lethargy.

For example, if you use a potent CBD product, CBD will bind to the enzyme, altering the effectiveness of all the medications you take afterward. The tighter the bond, the more competitive inhibition.

Different factors can reduce the enzyme activity, including how much CBD you take, your unique physiology, and the type of CBD you use. Whether you take CBD in the form of medical marijuana or use a CBD product without any THC also determines potential drug interactions you may encounter.

The Grapefruit Warning

One of the best things you can do to avoid potential interactions between CBD and other medications is to pay attention to the grapefruit warning. If a drug has such a warning on the bottle, the person using it should avoid consuming grapefruit.

The reason for it is that grapefruit interferes with the CYP3A4 enzyme. Several medications depend on this enzyme to break them down, transforming them from the inactive compound into the active one. If it is occupied by something else, the enzyme will turn the drug into the active compound much later, significantly altering its effect.

CBD also inhibits the CYP3A4 enzyme, so it can change the way your over-the-counter drug works. If you are currently taking medication for a specific physical or mental health condition, check if it has the grapefruit warning to estimate if it will interact with CBD.

Nevertheless, do not treat this method as a straightforward way to determine if you will experience any drug interactions. To stay completely safe, consult your doctor instead.

If you ever asked yourself, ‘How will CBD interact with my current medication?’, now you should know the answer. While CBD use is a generally safe practice, you should not overlook potential complications it may create.

Taking CBD, much like any other medication, requires a certain level of caution. When taken with other prescription drugs or over-the-counter medications, it might potentially increase side effects or produce entirely new ones. For example, if you use it with antiepileptic drugs (AEDs), your doctor will most likely monitor serum AED levels and LFTs during treatment, as CBD can interact with these substances.

Remember that a consultation with a health professional can only be beneficial. Thanks to it, you will learn what exactly can work in your case and what substances you should avoid.

Sources:

1. https://sites.psu.edu/cannabinoid/files/2020/06/NTI-Meds-to-be-Closely-Monitored-when-Co-Administered-with-Cannabinoids_2020_04_25.pdf
2. https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16355
3. https://www.statista.com/statistics/780284/levothyroxine-prescriptions-number-in-the-us/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546947/