CBD and Zoloft: Interactions and Side Effects

cbd and sertraline
By Alexandra Arnett Updated March 8th

Medically reviewed by Dr. Brian Kessler, MD

Fact-checked by Deb Tharp

Zoloft is a medication commonly prescribed to treat a number of mental health conditions involving depression and anxiety. 

Based on data from the National Institute of Mental Health Disorders, approximately 9.5% of adults in the United States experience depressive illnesses each year. Additionally, around 19% of adults suffer from anxiety disorders each year. 

The number of prescriptions for Zoloft or sertraline in the United States has increased by 10 million between 2004 and 2020. As of 2020, prescriptions for Zoloft or sertraline in the United States total 38.22 million. 

Some individuals seeking alternatives to prescription medication look to CBD. Our 2022 Annual Cannabis Conditions Report, which surveyed over 211,000 medical cannabis patients, found that roughly 19% of medical cannabis patients use cannabis for anxiety, and around 12% of medical cannabis patients use cannabis for PTSD.

It shouldn't come as a surprise that plenty of people are curious if it's safe to use CBD and Zoloft together. Unfortunately, the answer is murky and complex, but information is available to help people make the right decision for themselves.

The Complete Guide to Medical Cannabis for Stress & Anxiety

Find natural, lasting relief with our comprehensive (and completely free) patient’s guide to medical cannabis for stress and anxiety.

What is Zoloft?

Sertraline, the generic name for Zoloft, is classified as a selective serotonin reuptake inhibitor (SSRI). This type of antidepressant medication is relatively new and functions by blocking the brain from reabsorbing serotonin, enabling more serotonin to accumulate, and alleviating various symptoms linked to low serotonin levels. Many of these symptoms are linked to depression and anxiety.

The FDA has approved Zoloft for adults seeking treatment for the following conditions:

  • Major Depressive Disorder (MDD)
  • Obsessive-Compulsive Disorder (OCD)
  • Panic Disorder
  • Posttraumatic Stress Disorder (PTSD)
  • Premenstrual Dysphoric Disorder (PMDD)
  • Social Anxiety Disorder

In addition, Zoloft has the potential to help manage several disorders, such as body dysmorphic disorder, binge eating disorder, bulimia nervosa, premature ejaculation, and generalized anxiety disorder. 

The most common side effects in adults treated with Zoloft include:

  • Agitation
  • Anxiety
  • Diarrhea
  • Change in sleep habits, including increased sleepiness or insomnia
  • Fatigue
  • Increased sweating
  • Loss of appetite
  • Nausea or indigestion
  • Sexual problems
  • Tremors

Like many antidepressants, Zoloft is associated with an increased risk of suicidal thoughts in adults with major depression. It's important to note that taking too much Zoloft can lead to serotonin syndrome, which can cause muscle spasms, sweating, tremors, overactive reflexes, delirium, and hyperthermia.

Exercise caution when using Zoloft; this is particularly important for patients over 65. Some adverse side effects, such as inappropriate antidiuretic hormone, can cause your body to retain water, which may lead to hyponatremia, an increase in sodium levels in the blood. These conditions are treatable if caught early, but severe cases can lead to serious complications, including loss of consciousness, hallucinations, coma, brain herniation, or even death. 

Zoloft may also pose risks for pregnant women, potentially causing heart defects in infants and leading to prolonged hospitalization, tube feeding, and the need for respiratory support. It's important to discuss any concerns with your healthcare provider to determine the best course of treatment.

CBD and Zoloft: How Do They Interact?

CBD and Zoloft interaction

The CYP2C19 enzymes play a crucial role in processing both Zoloft and cannabinoids, such as CBD, in the liver. However, it's important to note that CBD has the potential to inhibit these enzymes. This inhibition could interfere with the body's ability to effectively metabolize drugs that rely on the CYP2C19 enzyme, like Zoloft. This enzyme interaction can lead to an increase in the levels of Zoloft present in a patient's system and can lead to an increase in adverse side effects, such as diarrhea, dizziness, and fatigue.1 Therefore, it's important to be mindful of the potential risks when taking CBD and other medications simultaneously. 

A PTSD study conducted on animals in 2021 found that CBD, when used alone or along with sertraline, helped regulate behavioral and neurochemical changes.2 While there is limited clinical evidence surrounding CBD for depression, current research does suggest that CBD may help improve some symptoms of depression. A new study published in April of 2023 found that, in mice, CBD alone produced a more significant antidepressant effect than CBD and sertraline combined or sertraline alone. However, since the researchers conducted this study on mice, more human clinical trials are needed to assess the efficacy and safety of using CBD for depression.3

Based on the current data available, more research is needed to determine the safety and efficacy of using Zoloft and CBD simultaneously. Still, so far, the results are promising. Individuals should consult their doctor before combining Zoloft and CBD. It is typically advised to space the use of CBD and Sertraline to approximately two hours apart.

Can I Take CBD with Zoloft?

There are differing opinions regarding the safety of combining CBD and Zoloft. Some online sources suggest that there have been no reported interactions, while others advise caution. 

It's worth noting that cannabinoids, such as CBD, are known to inhibit the CYP2C19 enzyme, which is also responsible for metabolizing prescription medications like Zoloft.

So, who is right? Can you take CBD with Zoloft? 

The potential interaction between CBD oil and SSRIs is an important topic to consider when discussing the use of both substances. Research indicates that because the CYP2C19 enzymes metabolize both Zoloft and CBD, the use of cannabinoids like CBD along with Zoloft may lead to an increased concentration of Zoloft in the system, which can result in serotonin syndrome or other adverse side effects such as diarrhea, dizziness, and fatigue.

Can CBD be a Viable Alternative for Zoloft?

Cbd vs zoloft

Data from our 2022 Annual Cannabis Conditions Report, collected from over 211,000 medical cannabis patients, indicates that 18.86% of patients were using cannabis for anxiety, and 12.39% were using it for PTSD. Depression isn't a qualifying condition for medical cannabis in many states, which has limited available data.

These findings back up an online survey study from 2018 that gathered responses from 2409 individuals, with over 60% stating they were utilizing CBD for a medical condition. The top three conditions that individuals reported using CBD for included pain, anxiety, and depression.4

Clinical trials assessing the anti-anxiety effects of CBD were first conducted in 1974 and 1982, with positive results demonstrating the efficacy of CBD for anxiety. Since then, a number of clinical trials have taken place demonstrating the same result: that CBD significantly reduces subjective anxiety. 

Furthermore, research on synthetic cannabinoid products like nabiximol, which has a 1:1 ratio of THC to CBD at 2.7mg and 2.5mg, has also been shown to be effective in reducing anxiety symptoms. More recently, research has also turned its attention to CBD and PTSD, with daily CBD doses ranging from 300mg to 600mg.5 

When it comes to tolerance of CBD, it is much different than building a tolerance to THC. Tolerance is defined as an individual's diminished response to a drug after repeated use. While much of the research has typically stated that CBD does not build a tolerance, one study from 2021 points to the possibility that after repeatedly taking high doses of CBD, a tolerance can build after around seven months.6 However, this is just one study, and more research is needed to confirm the ability of CBD to create a tolerance.

Unlike CBD, THC may cause anxiety when taken in high doses. While individuals each have a unique endocannabinoid system, paranoia and anxiety are commonly reported side effects of using high-THC products. It is recommended to start off using lower-THC products if you are trying to help relieve symptoms of anxiety. 

In addition to cannabinoids, it's important to consider the terpenes found in cannabis as they may be working in tandem with or independently from cannabinoids like CBD to alleviate symptoms of anxiety and depression. Terpenes, such as myrcene and linalool, have demonstrated anti-anxiety effects, while limonene and pinene can create a more alert and energetic effect, boosting an individual's mood.7

When comparing the long-term side effects of CBD vs. antidepressants, the long-term use of prescription medications, such as Zoloft or sertraline, may result in unwanted adverse side effects like memory issues, weight gain, and sexual dysfunction. In some cases, side effects may even include suicidal thoughts. 

Limited evidence exists to support any long-term adverse side effects of CBD. Some individuals may find relief by using CBD for conditions like anxiety, depression, and PTSD. If you are taking Zoloft or Sertraline and are considering incorporating or switching to CBD, it is important to consult with a psychiatrist before making any changes to your treatment regimen, like reducing or tapering off of Zoloft or Sertraline.

The Complete Guide to Medical Cannabis for Stress & Anxiety

Find natural, lasting relief with our comprehensive (and completely free) patient’s guide to medical cannabis for stress and anxiety.

References

  1.  MacCallum CA, Lo LA, Boivin M. "Is medical cannabis safe for my patients?" A practical review of cannabis safety considerations. European Journal of Internal Medicine. 2021;89:10-18. doi:https://doi.org/10.1016/j.ejim.2021.05.002
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  2.  Gasparyan A, Navarrete F, Manzanares J. Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD. Frontiers in Pharmacology. 2021;12. doi:https://doi.org/10.3389/fphar.2021.694510
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  3.  García-Gutiérrez MS, Navarro D, Austrich-Olivares A, Manzanares J. Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model. Frontiers in Pharmacology. 2023;14. doi:https://doi.org/10.3389/fphar.2023.1171646
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  4.  Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis Cannabinoid Res. 2018;3(1):152-161. Published 2018 Jul 1. doi:10.1089/can.2018.0006
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  5.  García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules. 2020;10(11). doi:https://doi.org/10.3390/biom10111575
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  6.  Uliel-Sibony S, Hausman-Kedem M, Fattal-Valevski A, Kramer U. Cannabidiol-enriched oil in children and adults with treatment-resistant epilepsy-does tolerance exist? Brain and Development. 2020;43(1). doi:https://doi.org/10.1016/j.braindev.2020.06.018
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  7.  Ferber SG, Namdar D, Hen-Shoval D, et al. The "Entourage Effect": Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Current Neuropharmacology. 2020;18(2):87-96. doi:https://doi.org/10.2174/1570159x17666190903103923
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The information in this article and any included images or charts are for educational purposes only. This information is neither a substitute for, nor does it replace, professional legal advice or medical advice, diagnosis, or treatment. If you have any concerns or questions about laws, regulations, or your health, you should always consult with an attorney, physician or other licensed professional.

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