Is it Safe to Take CBD with Metoprolol, Melatonin, Zoloft, and Zyprexa?

In our latest question and answer our pharmacist discusses if CBD interacts with metoprolol, melatonin, zoloft, and zyprexa.
Is it Safe to Take CBD with Metoprolol, Melatonin, Zoloft, and Zyprexa?

Brandon Asked

I'm on metoprolol er 25mg melation 5mg zoloft 50mg and zyprexa 5mg and I wondering if I can replace cbd with them or can I die if I take cbd with them my body isn't responding to them


There is limited data available on CBD's potential to cause interactions with sertraline (Zoloft), olanzapine (Zyprexa), and Melatonin..
CBD may inhibit metabolic enzymes involved in the metabolism of all three of these medications but, the chances of CBD causing a clinically significant interaction with any of these meds is rather low
Be sure to let your psychiatrist or doctor that manages your medications know that you're using CBD.


Hi Brandon and thanks for your question. Let's look at each medication you mentioned in your question individually and see whether or not they interact with CBD. 

Does CBD Interact with Metoprolol?

Metoprolol is a medication that belongs to a class of drugs known as beta blockers. It is used to treat high blood pressure and heart failure. Metoprolol works by blocking natural hormones in the body (norepinephrine and epinephrine) from binding to receptors in the heart and blood vessels. This results in decreased heart rate, blood pressure, and more relaxed blood vessels. 

There aren't any known drug interactions between CBD and metoprolol. That being said if you're using a full-spectrum CBD product that could contain small amounts of THC, which could counteract the effects of metoprolol by increasing your heart rate. 

Does CBD Interact with Melatonin?

Melatonin is a natural hormone produced by the brain in response to darkness. It's also a popular natural supplement that is known to help maintain the body's circadian rhythm (sleep cycle). 

Melatonin is metabolized by enzymes in the liver particularly the enzymes CYP1A1 and CYP1A2. There's a theoretical chance that CBD could impact (increase or decrease) the metabolism of melatonin, by interfering with CYP1A2, but this isn't something I'd worry about because CYP1A2 is not the most important enzyme for CBD metabolism and because both CBD and melatonin are usually very well tolerated.

Does CBD Interact with Zoloft (sertraline)?

We've actually addressed this interaction in another one of our previous questions. You can find that question here! Or keep reading below for a summary of that answer. 

Zoloft or sertraline is a medication used to treat depression and other psychiatric disorders. It belongs to a class of medications called Selective Serotonin Reuptake Inhibitors or SSRIs. Zoloft is the most commonly prescribed antidepressant medication in the United States.

Sertraline is metabolized by a number of CYP enzymes present in the liver including CYP2B6 and to a lesser extent CYP2C19, CYP2C9, CYP3A4, and CYP2D6. According to the manufacturer’s package insert for sertraline, that’s reviewed by the FDA, dose reductions may be warranted in patients treated with sertraline that are taking other drugs metabolized by these enzymes. 

CBD is also metabolized by CYP enzymes in the liver, so using CBD may alter the way these enzymes function in regard to their ability to metabolize other drugs such as sertraline.

According to the package insert for the FDA-approved CBD oral solution, CBD is metabolized by CYP3A4 and CYP2C19, and has the potential to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19. Therefore, because CBD can inhibit some of the same enzymes that’re responsible for the metabolism of sertraline, there’s a possibility that CBD could reduce the metabolism of sertraline leading to increased concentrations of the drug in the body increasing the risk of adverse effects due to sertraline.  

Does CBD Interact with Zyprexa (olanzapine)?

Zyprexa or olanzapine is a medication used to treat psychiatric disorders. It is also, commonly used off-label for the treatment of chemotherapy-induced nausea and vomiting. 

Just like with melatonin, Zyprexa is also metabolized in the liver by CYP1A2 enzymes.  CYP1A2 is responsible, to a small extent, for the metabolism of CBD. So, again, just like with melatonin there's a theoretical chance that CBD could (increase or decrease) the metabolism of zyprexa, by interfering with CYP1A2. 

I wouldn't be that concerned with this interaction because CYP1A2 plays only a minor role in the metabolism of CBD. 

"Cannabidiol may induce or inhibit CYP1A2 " -Epidiolex (Cannabidiol) [Package insert]


In summary, CBD is prone to interact with Zoloft, Melatonin, and Zyprexa, but unless you’re consistently using high doses of CBD (upwards of 100 mg multiple times per day) I wouldn’t worry too much about it. I suggest letting your doctor or psychiatrist that prescribes these medications know that you're using CBD. That way they can monitor for any changes or adverse effects from changes in the metabolism of any of these medications you're taking. 

  1. Epidiolex. Carlsbad, CA: Greenwich Biosciences; 2018. [package insert] [package insert].
  2. Zoloft. New York, NY: Pfizer; 2016. [package insert] [package insert].
  3. Zyprexa. Indianapolis, IN: Eli Lilly; 1996 [package insert] [package insert].
  4. Melatonin. Bridgewater, NJ: Safrel; 2020 [package insert] [package insert].
  5. Lopressor. East Hanover, NJ: Novartis; 2008. [package insert] [package insert].

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