CBD and drug interactions can be complicated to understand. Over the past decade, the possible health benefits of CBD have garnered a great deal of attention. Researchers, doctors and patients have begun to explore CBD in the hopes of finding something to augment the conventional medications currently available.

However, it is important to note that CBD can change the way that your body metabolizes some prescription medications. CBD might alter your body’s ability to break certain medications down, leading to higher than normal amounts entering your bloodstream.

In rare cases, this change of metabolism can mean that less of a medication enters your bloodstream, making it less effective.

Before you add CBD, or any other supplement, to your current regimen, go over the possible risks and benefits with your healthcare team. It’s important to always follow their recommendations.

Let’s go over the basics of drug metabolism so that you have a better understanding of how CBD might affect you.

CBD and Drug Interactions

Cytochrome P450 Enzymes Even when it seems that your body is at rest, there are trillions of chemical reactions going on every second. Without these chemical reactions, all of your cells would starve, run out of oxygen or be poisoned by their own waste. What powers a lot of this activity are natural chemicals called enzymes. Most enzymes are protein chains and they function to speed up chemical reactions. Without this enzymatic action, most reactions would happen too slowly to do your body any good. The majority of drugs are broken down by what’s called Cytochrome P450 (CYP450) enzymes. There are over 50,000 distinct enzymes in this group that are found in tissues throughout your entire body. However, for this discussion, we’ll focus on CYP450s found in your gut and liver. Over 60% of prescription medications are metabolized by CYP450 enzymes.

Drug Metabolism Basics When you swallow a medication, it first travels to your stomach. The stomach really isn’t very efficient at absorbing things, so most medications just pass through. Next, it enters your small intestine where CYP450 enzymes begin to break it down. The medication is absorbed into your bloodstream and then travels directly to your liver through your hepatic portal vein. Inside the liver, more CYP450s break the medication down further. After traveling through the liver, the medication then enters your systemic bloodstream that circulates throughout the rest of your body. As the medication travels throughout your systemic bloodstream, it eventually passes back through the liver. During each pass, more and more of the medication is cleared from your blood until it is completely eliminated from your body.

The First Pass Effect and Bioavailability When you take medications orally, not all of the active ingredient you swallow will make it into your systemic bloodstream. A certain amount is lost because CYP450 enzymes break it down before it leaves the digestive system and liver. This is known as the first pass effect. Medication dosage is designed to take this loss into account. The measure of how much of a drug enters your systemic bloodstream is known as the bioavailability of a drug. It’s expressed as a percentage. So if a drug has a bioavailability of 75%, that means 25% is lost and 75% makes it through to the systemic bloodstream.

Grapefruit and the First Pass Effect You may have noticed a warning on certain medication that states, “Avoid eating grapefruit or drinking grapefruit juice while taking this medication.” The reason for this warning is that compounds found in grapefruit, called furanocoumarins, can inhibit the actions of some CYP450 enzymes in your gut. Grapefruit mostly affects the CYP450 enzyme CYP3A4, which metabolizes 60% of prescription medications. The furanocoumarins bind to CYP3A4 in your small intestine and effectively neutralize it. This means that less of the medication is destroyed and so more enters your liver. Your liver can only metabolize so much at once, which means more of the medication may pass unchanged into your systemic bloodstream.

What CBD and Grapefruit Have in Common CBD can also have effects on the way your body metabolizes certain prescription medications. Researchers found that CBD is a powerful inhibitor of important CYP450 enzymes. It’s thought that CBD binds to CYP450s in both the gut and the liver, increasing the likelihood that it will impact drug metabolism. Furanocoumarins from grapefruit only affect enzymes in the small intestine. But, if CBD affects enzymes in the liver as well, this would make for an even greater chance of drug interactions than even grapefruit. It is advised that you do not combine CBD with any drug that carries a grapefruit warning without the knowledge, consent and strict supervision of your healthcare team. Ask your doctor or pharmacist if you should avoid grapefruit or grapefruit juice while taking any of your medications.

How Does CBD Affect Drug Metabolism? Unfortunately, research is still playing catch up with regards to how CBD can affect drug metabolism. The exact mechanism of how CBD changes the way your body processes drugs is not yet fully understood. It’s been theorized that CBD binds to the active site of enzymes. The active site is the part of the protein chain that attaches to a substrate, in this case a drug, and carries out its chemical reaction. If the active sites on the enzymes are bound up by CBD, they’re not available to bind to medications moving through the gut and liver. Also, it’s believed that this effect does not simply wear off over time. Once bound, your enzymes stay bound, permanently. You then have to wait for your body to make a new batch of enzymes in order for drug metabolism to return to normal. This can take as much as 72 hours. CBD has been shown to inhibit CYP3A4, CYP3A5 and CYP2D6. All three of these enzymes play a major role in the metabolism of many prescription drugs.

What Can be the Effect of CYP450 Inhibition? If some of the CYP450s in your gut and liver have been bound up by CBD, then they are not available to break down medications as they move through your system. This means that higher than normal doses can enter your systemic bloodstream. This has the potential to turn a therapeutic dose of medication into a dangerous overdose, especially for drugs with a narrow therapeutic window. Medications like this have to be dosed very, very carefully. Too small a dose and the medicine is ineffective. Too large a dose, even just by a small amount, and it’s toxic. Enzyme inhibition can also mean that it takes longer for your body to clear medications from your blood. If CBD changes the way that your body metabolizes drugs, it could mean that you are at a higher risk for adverse effects from your medications.

Alcohol Alcohol metabolism is not dependent on CYP450 enzymes. There no known interaction that would lead you to become more intoxicated, or slow your ability to clear alcohol from you blood, by combining the two. It could also be that CBD can help lower your blood alcohol levels and possibly protect your brain from damage while you are intoxicated. To learn more about the scientific research on CBD and alcohol, check out the article below. CBD and Alcohol

Aminoketone Antidepressants Wellbutrin is currently the only aminoketone antidepressant available on the market. It is not fully understood how Wellbutrin counteracts depression. It is chemically unrelated to other kinds of antidepressants like selective serotonin reuptake inhibitors or tricyclic antidepressants. Wellbutrin is metabolized in the liver by CYP2B6. CBD has been shown to inhibit this enzyme. Mixing CBD and Wellbutrin should not be attempted without medical supervision. To learn more about the scientific research on CBD and Wellbutrin, check out the article below. CBD and Wellbutrin

Antibiotics Antibiotics inhibit the growth of certain bacterias, allowing for the immune system to better fight them off. Whether or not it is safe to combine CBD and a given antibiotic depends on how the body metabolizes that specific medication. Some antibiotics are not metabolized by CYP450s that are affected by CBD, but others are. Macrolide antibiotics in particular could interact with CBD. It is best to discuss your CBD use with your doctor and proceed with caution when combining CBD and antibiotics. To learn more about the scientific research on CBD and antibiotics, check out the article below. CBD and Antibiotics

Atypical Antipsychotics Atypical antipsychotics are prescribed to treat the symptoms of conditions like schizophrenia, bipolar disorder and major depressive disorder. These medications help to calm overactive dopamine signals in the brain. This can help lessen symptoms like paranoia, hallucinations and/or delusions. Both quetiapine (Seroquel) and olanzapine (Zyprexa) are metabolized by CYP450 enzymes in the liver. Both drugs carry a grapefruit warning, and as such, should not be combined with CBD without medical supervision. Studies have found that CBD may be helpful in treating the symptoms of psychosis in its own right. To learn more about the scientific research of interactions between CBD and quetiapine, CBD and seroquel, or CBD and zyprexa, check out the articles below. CBD and Quetiapine

CBD and Seroquel

CBD and Zyprexa

Anticoagulants Anticoagulants are meant to either prevent or treat blood clots in your circulatory system. The majority of these medications are metabolized by CYP3A4 and CYP3A5. CBD may inhibit both of these enzymes. Adverse effects from these medications could be life threatening or even fatal. You absolutely should not add CBD to your current regimen without medical supervision. To learn more about the scientific research of interactions between CBD and xarelto, CBD and warfarin, or CBD and eliquis, check out the articles below. CBD and Xarelto

CBD and Warfarin

CBD and Eliquis

Anticonvulsants Anticonvulsants work by calming overactivity in the brain that can lead to seizure. There are no known interactions between CBD and gabapentin (Neurontin) or lamotrigine (Lamictal). Neither of these medications is metabolized by CYP450 enzymes. However, anticonvulsants like zonisamide (Zonegran) and carbamazepine (Tegretol) are metabolized by CYP3A4. So there is a potential for them to interact with CBD. Continued research has shown that CBD may be able to help relieve some of the same symptoms as these medications. To learn more about the scientific research of interactions between CBD and gabapentin, CBD and lamictal, or CBD and tegretol, check out the articles below. CBD and Gabapentin

CBD and Lamictal

CBD and Tegretol

Antimanic Agents Lithium has been a mainstay for the treatment of mental health conditions since the mid-twentieth century. Despite this, it’s exact mechanism of action is still not completely understood. It has mood stabilizing properties that are useful in the treatment of conditions like major depressive disorder and bipolar disorder. There are currently no known interactions between lithium and CBD. Studies have found that CBD also has a calming effect on the brain that might be able to help with symptoms like manic episodes. Research has found that CBD can mimic the actions of the neurotransmitter gamma-Aminobutyric acid (GABA), which acts as a calming agent for the central nervous system. To learn more about the scientific research of interactions between CBD and lithium check out the article below. CBD and Lithium

Anti-Nausea Medications The anti-nausea medication ondansetron (Zofran) works by blocking the the neurotransmitter serotonin from binding to its receptors. Stopping the activity of serotonin has been shown to decrease nausea and vomiting in both animal and human studies. It is potentially dangerous to mix CBD and Zofran. Zofran is metabolized by CYP2D6 and CYP3A4. CBD inhibits both of these enzymes and so can increase the amount of Zofran that enters your bloodstream. It may also slow down your body’s ability to clear the drug from your system. This could lead to life threatening or even fatal side effects, such as serotonin syndrome. You should not combine CBD and Zofran without the supervision of your healthcare team. To learn more about the scientific research of interactions between CBD and Zofran check out the article below. CBD and Zofran

Benzodiazepines Benzodiazepines are sedatives commonly prescribed to treat symptoms of conditions like anxiety disorders or as muscle relaxers. Benzodiazepines are metabolized by CYP450 enzymes and carry grapefruit warnings. CBD can potentially increase the amounts of these medication in your bloodstream and slow their clearance from your system. Benzodiazepines mimic the actions of the neurotransmitter GABA. CBD has been found to have a similar effect and so may also be able to help manage the symptoms of anxiety disorders. Do not combine these medications with CBD without medical supervision. To learn more about the scientific research of interactions between CBD and Xanax, CBD and Ativan, or CBD and Valium check out the articles below. CBD and Xanax

CBD and Ativan

CBD and Valium

H2 Receptor Blockers H2 receptor blockers treat the symptoms of gastroesophageal reflux disease (GERD), which causes excess amounts of stomach acid that can travel up the esophagus. They can also work like an antihistamine and help treat allergic reactions. H2 receptor blockers are metabolized in the liver by CYP450 enzymes and may interact with CBD. You should not combine CBD and an H2 blocker without discussing it with your doctor.

Over-the-Counter Meds Over-the-counter medications that contain non-steroidal anti-inflammatories (NSAIDs), like aspirin or acetaminophen, could potentially interact with CBD. Many over-the-counter medicines are metabolized by CYP450 enzymes. Higher than normal doses, coupled with slowed drug clearance, could have dangerous side effects, like liver damage. Talk to your doctor or pharmacist before combining these medications with CBD. To learn more about the scientific research of interactions between CBD and NyQuil, or CBD and Excedrin check out the articles below. CBD and NyQuil

CBD and Excedrin

Prescription Non-Steroidal Anti-Inflammatories Prescription strength NSAIDs are also commonly metabolized by CYP450 enzymes. It could be unsafe to mix CBD and these medications. CBD has also been shown to have anti-inflammatory and neuroprotective properties. It may be able to help manage chronic inflammation. To learn more about the scientific research of interactions between CBD and Mobic check out the articles below. CBD and Mobic

Prescription Sleep Aids Prescription sleep aids are meant to treat the side effects of short-term and chronic insomnia. Zolpidem (Ambien) is a powerful non-benzodiazepine hypnotic. It mimics the actions of the neurotransmitter GABA. It calms the mind, allowing the patient to fall asleep. It is extensively metabolized in the liver by CYP3A4 with CYP2D6 also playing a minor roll. As such, it may interact with CBD, possibly increasing unwanted side effects. You should combine CBD and zolpidem without medical supervision. Studies have found that CBD can also mimic the actions of GABA. So CBD may also help relax the mind and allow for a more restful night.

Proton-Pump Inhibitors Proton-pump inhibitors help to cut back on the production of stomach acid. This helps to manage the symptoms of conditions like stomach ulcers and acid reflux. There are currently no known interactions between CBD and the proton-pump inhibitor Omeprazole. To learn more about the scientific research of interactions between CBD and Omeprazole check out the articles below. CBD and Omeprazole

Selective Serotonin Reuptake Inhibitors SSRIs are antidepressant medications that stop the central nervous system from breaking down the neurotransmitter serotonin. SSRIs are commonly prescribed to treat mental health conditions like seasonal affective disorder and major depressive disorder. SSRIs are metabolized by CYP450 enzymes. This could lead to higher than normal amounts of the medication in your bloodstream and slow clearance. This could mean increased side effects from these medications, including dangerous ones like serotonin syndrome. Combining CBD and SSRIs should only be done under the supervision of your healthcare team. To learn more about the scientific research of interactions between CBD and Lexapro, CBD and Effexor, CBD and Zoloft, CBD and Cymbalta, or CBD and Citalopram check out the articles below. CBD and Lexapro

CBD and Effexor

CBD and Zoloft

CBD and Cymbalta

CBD and Citalopram

Statins Statins are medications used to lower levels of bad cholesterol (LDL) in your blood. Some statins are metabolized by CYP450 enzymes, and others are not. So some could interact with CBD, and others might not. Statins like Lipitor and Zocor are indeed metabolized by CYP3A4 and may interact with CBD. If you are taking a statin, speak with your healthcare team before adding CBD. To learn more about the scientific research of interactions between CBD and Statins, or CBD and Lipitor check out the articles below. CBD and Statins

CBD and Lipitor

Steroidal Medications Steroidal medications are commonly prescribed to beat back inflammation in the body. Depending on the medication, CBD could affect the way your body metabolizes steroid medications. In some cases, it could cause higher than normal levels of a steroid to enter your bloodstream. In other cases, it could lower the levels of steroidal medications in your blood, making them less effective. CBD has also been shown to have anti-inflammatory properties. In animal studies, CBD hampered the production of cytokines, proteins that activate inflammatory responses in the body. To learn more about the scientific research of interactions between CBD and Prednisone check out the articles below. CBD and Prednisone

Stimulant Medications Stimulant medications can help manage the symptoms of attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) in children and adults. Some stimulant medications, like Ritalin, are not metabolized by CYP450 enzymes. So there may be no interaction with CBD. However, other stimulant drugs like Adderall and Vyvanse, are metabolized by CYP2D6. Studies have shown that CBD does inhibit the actions of this enzyme which could cause higher than normal amounts of the drug in your bloodstream. Discuss adding CBD to your current regimen with your healthcare team and follow their recommendations. CBD may be able to help ADD/ADHD symptoms. CBD may be able to increase neurotransmitters in the brain like dopamine and anandamide. This may help a person with ADD/ADHD to have better focus. To learn more about the scientific research of interactions between CBD and Ritalin, or CBD and Vyvanse check out the articles below. CBD and Ritalin

CBD and Vyvanse

Supplements Whether or not CBD interacts with over-the-counter supplements depends on how they are metabolized by the body. Supplements that aren’t metabolized by CYP450s should not interact, but one should still proceed with caution. You shouldn’t mix CBD and supplements without first discussing it with your doctor. In the case of kratom, it does not directly interact with CBD. However, since kratom is also a powerful inhibitor of CYP450 enzymes, mixing CBD with kratom has the potential to greatly diminish your ability to metabolize medications. It is not advisable to mix CBD and kratom if you are also taking other medications, even over-the-counter ones. To learn more about the scientific research of interactions between CBD and Kratom check out the articles below. CBD and Kratom

Conclusions Drug interactions can be complex to understand and take many years of research to pinpoint. Unfortunately, science is still catching up to when it comes to CBD and which drugs it can affect. Studies have found that CBD can interact with some medications, the extent of which still has not been determined. For now, the best guide to go by is whether or not a medication carries a grapefruit warning. You should not mix CBD and medications with grapefruit warnings without discussing it with your doctor. It’s important to always follow your healthcare team’s recommendations. Written by Katherine Morgan