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Is it Safe to Use CBD and Zoloft (sertraline) at the same time?

In our latest question and answer, the medical cannabis pharmacist discusses if it is ok to use CBD oil while taking sertraline.

Answered by: Dr. Geoffrey Brown, PharmD

Khia Asked

I take Zoloft for my depression and would like to start supplementing CBD to reduce inflammation and help with anxiety. Is it safe to use with Zoloft?


There is limited data available on CBD’s potential to cause interactions with sertraline (Zoloft).
CBD may inhibit metabolic enzymes involved in the metabolism of sertraline but, the chances of CBD causing clinically significant interactions with sertraline are rather low.
Be sure to let your psychiatrist or doctor that manages your sertraline therapy know that you’re using CBD.


Hi Khia, and thank you for your question. While I couldn’t find any studies investigating this interaction in particular, I was able to find some information regarding the metabolism of both of drugs which can help us answer questions about the likelihood of an interaction.

In short, CBD may inhibit some of the enzymes that’re involved in the metabolism of sertraline (Zoloft). Therefore, theoretically, there is a possibility the two could interact. However, the likelihood that this interaction would be clinically significant or something you need to be concerned with is rather low.

Sertraline (Brand name Zoloft) is a selective serotonin reuptake inhibitor or SSRI and 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.

Cannabidiol (CBD) is the primary non-euphoric cannabinoid in cannabis/hemp and is now a common ingredient in many health and consumer products. One of the most commonly claimed indications for CBD is anxiety. Preliminary evidence suggests CBD shows promise as a potential treatment for anxiety, but the doses researched vary greatly between studies.

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.

While there’s certainly a theoretical basis for this interaction, I would not be too concerned about this from a safety standpoint for two reasons. For one, the blood concentrations of CBD needed to inhibit these enzymes aren’t likely to be achieved by CBD taken at usual doses. The second reason is because multiple CYP enzymes are responsible for the metabolism of sertraline it would be difficult for CBD alone to cause a serious interaction by interfering with just one or even a couple of those enzymes. That being said, i t’s still a good idea to let your doctor of psychiatrist that manages your sertraline therapy know that you’re using CBD. That way they can monitor for any changes or adverse effects from changes in sertraline metabolism.

To summarize, there’s a possibility an interaction between CBD and sertraline could occur, 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 hope this helps answer your question.

Thanks again Khia. Please don’t hesitate to reach out again in the future with any cannabis questions you have.


Zoloft [package insert]. New York, NY: Pfizer, Inc. 2016.

Epidiolex [ package insert ]. Carlsbad, CA: Greenwich Biosciences, Inc. 2020.

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