In our latest question and answer, the pharmacist discusses whether or not Zoloft (sertraline) interacts with CBD (cannabidiol). Zoloft (Sertraline) is used to treat depression and other mental conditions. Read here to know the interaction between CBD and Zoloft. CBD is a popular alternative treatment for anxiety and depression, but will it help or worsen the side effects of sertraline (Zoloft) if used together?
Does CBD Interact With Zoloft (Sertraline)?
In our latest question and answer, the pharmacist discusses whether or not Zoloft (sertraline) interacts with CBD (cannabidiol).
I currently take 50mg of Sertraline, I have tried increasing Sertraline but I don’t like the side effects. The 50mg of Sertraline has improved my overall mood but I still feel anxious. Would it be safe to also use CBD oil alongside Sertraline?
At a glance
- Drug interaction studies with CBD are lacking, but preliminary evidence suggests a variety of potential interactions based on what we know of CBD metabolism.
- The chance of CBD having a clinically significant interaction with Zoloft (sertraline) is low based on available data.
Cannabidiol, also known as CBD, is a major component of cannabis (i.e. marijuana).
While THC (delta-9-tetrahydrocannabinol) is likely more well-known due to its psychoactive and euphoric effects, CBD makes up almost 40% of cannabis extracts and has a wide range of potential benefits when used medicinally, although more studies are certainly needed to better understand the compound.
While the exact dosing of CBD explored in studies ranges wildly (from 1 mg to over 600 mg), there is preliminary positive evidence for a variety of indications, including:
- Multiple Sclerosis
- Parkinson’s Disease
Further adding to the potential benefit of CBD, is the fact that it is considered CBD is considered “non-euphoric”, even at high doses.
CBD has recently exploded in popularity, with multiple products and brands available at a number of natural health food and supplement stores. It is even being mixed with traditional consumer products, like water!
With this, it is important to consider potential drug interactions with prescription medication.
Due to the relatively recent nature of CBD use for medicinal purposes, there is a distinct lack of studies when it comes to potential drug interactions between CBD and prescription medication, like Zoloft (sertraline).
Zoloft – CBD (Cannabidiol) Interaction
Zoloft (sertraline), an SSRI (Selective Serotonin Re-uptake Inhibitor), is metabolized extensively by a variety of CYP enzymes, including:
As discussed above, research indicates that CBD can inhibit many of the metabolizing enzymes listed above.
Therefore, the use of CBD and Zoloft together could theoretically increase the risk of adverse effects, due to increasing Zoloft concentrations in the body.
However, additional data on CBD drug interactions indicate the risk of an interaction between CBD and Zoloft specifically is low.
There are many studies that postulate that while CBD does inhibit metabolizing enzymes, it is not significant and the blood concentrations needed to affect these metabolizing enzymes in humans far exceeds what is possible with usual dosing.
In addition, since Zoloft is metabolized in the body by a number of enzymes, it is thought that it would be difficult for a single agent to cause a clinically significant interaction. In the words of one study:
“The observation that multiple enzymes appear to be involved in sertraline [Zoloft] metabolism suggests that there should be no single agent that could substantially alter the pharmacokinetics of sertraline, nor should there be any single drug-metabolizing enzyme genetic polymorphism (e.g., CYP2D6, CYP2C19, CYP2C9, UGT1A1) that could profoundly impact the pharmacokinetics of sertraline.”
Nevertheless, until studies are completed that specifically look at how CBD interacts with Zoloft (sertraline), we can only make educated guesses. It would be prudent to let your doctor know you are interested in trying CBD, so you can be appropriately monitored, just in case.
CBD and Zoloft (Sertraline) – August 2022
According to Mayo Clinic, antidepressants are a popular treatment choice for depression. Although antidepressants may not cure depression, they can reduce the symptoms (4 ) .
Many types of antidepressant medications are available to treat depression, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Zoloft (sertraline) is an antidepressant that belongs to a group of SSRIs.
Enzymes are the proteins that speed up chemical reactions in the body and help with vital body functions like digestion and respiration.
CYP34A enzymes belong to the class of CYP450 or Cytochrome P450 enzymes, which is essential for the metabolism of many medications (5 ) .
An article by CBD Oil Review explains that CBD blocks the cytochrome P450 enzyme system’s ability to metabolize certain drugs, including SSRIs, resulting in an overall increase in processing times (6 ) . Thus, taking CBD supplements while on these medications could interfere with how the body absorbs these medications.
This mechanism mirrors that of the grapefruit as it inhibits the same set of liver enzymes, the CYP34A, that CBD blocks, according to an article published by Harvard Health Publishing (7 ) .
In an article on grapefruit juice and medications, also published by Harvard Health Publishing, grapefruit was shown to be dangerous when combined with some drugs used for high blood pressure, high cholesterol, and depression, as the fruit can impair how the body absorbs the drugs (8 ) .
When the CYP450 system’s ability to metabolize certain drugs is affected, a high concentration of drugs remains in the body at one time. This increased level can cause unwanted side effects and, sometimes, an overdose (9 ) .
Taking CBD oil with SSRIs may reduce the efficacy of the antidepressants, or inversely, the efficacy of CBD oil may be reduced by antidepressants (10 ) .
Still, there is no substantial evidence to suggest any definite adverse reaction that may occur when taking CBD oil together with SSRIs.
Stipulations are not definite because of limited research published on CBD and drug interactions.
Another reason for the lack of conclusive evidence is because CBD possesses anti-depressive characteristics of its own .
In a 2014 study published in the CNS & Neurological Disorders – Drug Targets Journal, CBD was shown to possess antidepressant-like and anxiolytic-like effects (11 ) .
Adverse interactions between CBD oil and antidepressants are rare (12 ) . However, seeking the advice of a physician or psychiatrist is recommended before combining the two substances.
Also, when taking medications that interact with CBD, consulting with a doctor is advised to ensure that supplementing a personal therapy with CBD oil is without risk. The doctor may have to adjust the dosage of the medications so that they can be safely used with CBD oil (13 ) .
Can Another Antidepressant Be a Substitute for Zoloft So CBD Oil Can Be Taken ?
Zoloft (sertraline) is an antidepressant that works by increasing levels of serotonin in the brain.
As a neurotransmitter, serotonin modulates the activity of the nervous system and a wide range of processes linked to brain function and behavior, as indicated in a review published in the Annual Review of Medicine in 2018 (14 ) .
SSRIs are called selective because they primarily impact serotonin, not other neurotransmitters. SSRIs inhibit the reuptake or reabsorption of serotonin into the neurons, making serotonin accessible to improve the transmission of messages between neurons.
Mayo Clinic lists the SSRIs approved by the FDA to treat depressio n (15 ) :
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluoxetine (Prozac)
- Paroxetine (Paxil, Pexeva)
- Sertraline (Zoloft)
There are fewer side effects and drug interactions with SSRIs than with other types of antidepressants, according to Mayo Clinic.
However, for the same reason that CBD could interfere with how the human body metabolizes SSRIs, replacing Zoloft with any of the drugs listed above is likely to cause the same metabolic impact.
Can CBD replace Zoloft?
A 2018 study published in the Frontiers in Immunology Journal demonstrated CBD as a potential remedy to depression (16 ) . In the study, researchers examined the experimental and clinical use of CBD and found that it showed anxiolytic (anti-anxiety), antiepileptic, and antipsychotic properties that may help reduce depression linked to stress.
CBD’s potential benefits for depression may be linked to its positive impact on serotonin receptors in the brain.
A 2018 study published in Progress in Neuro-Psychopharmacology & Biological Psychiatry Journal shows how antidepressant-like effects induced by CBD are dependent on brain serotonin levels (17 ) .
Researchers of a study , which was published in World Psychiatry Journal in 2015, found that impairing serotonin function can cause clinical depression in some circumstances (18 ) .
In another study , which was published in Frontiers in Neuroscience in 2018, it was shown that CBD might help treat a variety of psychological conditions, including mental health and post-traumatic stress disorder (PTSD) (19 ) .
Research published in Trends in Pharmacological Sciences in 2009 examined the therapeutic potential of the endocannabinoid system (ECS) (20 ) .
The ECS works to maintain balance among the essential functions of the body, including sleep, mood, appetite, and bowel movements.
The authors of that study concluded that the endocannabinoid system could be the target of “the development of a novel class of antidepressants.”
Researchers of another study , which was published in Neuropharmacology Journal in 2016, arrived at the same conclusion (21 ) .
CBD also appears to have some benefits over most antidepressant medications that take weeks to start working.
Researchers in a study published in the British Journal of Pharmacology found that CBD induced fast and sustained antidepressant-like effects in animal models comparable to those of imipramine, a tricyclic antidepressant (TCA) used mainly in the treatment of depression (22 ) .
However, there has been no study that would provide evidence that CBD can be used specifically to replace Zoloft.
Meanwhile, it is not advisable to stop taking prescribed medications, especially antidepressants, without talking to a healthcare provider first.
Medical experts caution against stopping taking sertraline, even when the person feels better. Missing doses of sertraline may increase the risk of relapse in symptoms, according to the National Alliance On Mental Illness (NAMI) (23 ) .
Abruptly stopping sertraline use may result in one or more of the following withdrawal symptoms:
- Having nightmares
- Prickling sensation on the skin
Before discontinuing sertraline intake or adjusting to low doses, work with a doctor or healthcare provider to devise a plan for gradually decreasing its dosage.
Even though CBD is becoming an increasingly popular alternative for a range of health issues, studies on how CBD may help with depression are limited. Thus, the best course of action is still to consult with a doctor before starting a CBD regimen.
What to Look for in a CBD Product
Zoloft interacts with CBD. Thus, consulting with a doctor is advised before supplementing a personal therapy with CBD oil. The doctor may consider adjusting the dosage of the medications so that they can be safely used with CBD oil (24 ) .
Full-spectrum CBD oil contains all phytonutrients from hemp, including trace amounts of THC, terpenes, flavonoids, and essential oils. Meanwhile, CBD isolates carry only pure, isolated cannabidiol.
Regardless of the form of CBD products that one chooses, careful consideration must be employed in selecting the best CBD oil to use, especially when trying to manage depression.
The following factors are essential to ensure the safety and reliability of the CBD products purchased:
- Research on the exact legal stipulations applicable to CBD in the area where it would be purchased and used.
- Purchase only high-quality CBD products from legitimate and reliable brands. The majority of companies that manufacture the best CBD oil products grow their own hemp from their own farm, or they purchase from licensed hemp producers.
- When buying from an online store, research product reviews. When buying from a physical store or dispensary, check whether the store is authorized by the government to sell CBD.
- One important thing to look for in CBD products is certification codes. Several certification authorities approve certain products only after some thorough screening tests.
- Compare company claims about their products’ potency with that of the third-party lab reports.
- Consulting with a trusted medical professional who is experienced in CBD use is ideal before one purchases his or her first bottle of CBD.
Depression vs. Anxiety Disorder
According to the Anxiety and Depression Association of America (ADAA) , depression and anxiety disorder are not the same. However, people with depression often experience symptoms comparable to those of an anxiety disorder, such as irritability, nervousness, and problems concentrating and sleeping (25 ) .
ADAA explains that each disorder has its own behavioral and emotional symptoms, as well as causes. Still, many people who have depression have a history of an anxiety disorder earlier in life.
Symptoms of both conditions usually improve with psychological counseling, medications, like antidepressants, or both.
In a 2914 study published in BMC Psychiatry Journal , researchers suggest that lifestyle changes like increasing social support, improving sleep habits, getting regular exercise, and using stress-reduction techniques may also help manage depression (26 ) .
However, alcohol, smoking, and recreational drugs can make depression and anxiety disorder worse and interfere with treatment, according to the authors of the study.
Having high blood pressure may also contribute to poor management of depression. Results of a 2013 study published in Experimental & Clinical Cardiology Journal suggest that depression is a typical feature in people experiencing uncontrolled high blood pressure (27 ) .
Screening for depression in people with high blood pressure is an easy and cost-effective tool that may improve results.
Zoloft (Sertraline) for Depression
A 1994 study published in Clinical Therapeutics Journal examined the role of sertraline in the management of depression (28 ) . Researchers concluded that this SSRI showed promise as a therapeutic alternative in the management of depression.
However, a study published in Lancet Psychiatry Journal recently has found that, despite being marketed as an antidepressant, sertraline may be unlikely to alleviate depressive symptoms within six weeks. Meanwhile, their data showed improvements in anxiety (29 ) .
The unexpected results prompted Professor Glyn Lewis, lead researcher and head of division at the University College London (UCL) Psychiatry, to say, “We definitely need better treatments for depression – we need more research in this area.”
Cannabidiol, more recognized as CBD, is becoming increasingly popular as a remedy for common ailments. It is one of the many chemical compounds known as cannabinoids found in the cannabis plant, which is also occasionally called hemp or marijuana, depending on the degree of tetrahydrocannabinol (THC) it contains.
THC is another cannabinoid that is linked to a “high,” being the psychoactive constituent of marijuana. Unlike THC, however, CBD keeps one alert and energetic. CBD counters the effects of THC by decreasing the level of stress or anxiety. Because of this action, CBD is frequently extracted to use distinctly for medical use that is non-psychoactive.
CBD oil is the undiluted liquid decoction of Cannabis sativa, a plant commonly known as marijuana. Consumers can purchase CBD oil separately and use it orally. CBD oil or tincture is a popular CBD product that one may purchase online like an over-the-counter supplement.
CBD continues to gain popularity as scientists discover more of its potential health benefits.
However, a Harvard Health article by Peter Grinspoon, M.D., author of the memoir Free Refills: A Doctor Confronts His Addiction warns that CBD use may potentially cause side effects, including irritability, nausea, and fatigue (30 ) . Also, CBD may increase the level in the blood of the blood thinners like coumadin, and it can raise levels of other prescription medications in the blood as well.
In its Consumer Update , the U.S. Food and Drug Administration (FDA) also warned against some CBD products that are being marketed with unsubstantiated medical claims and are of inferior or unknown quality (31 ) . Thus, choosing products carefully is essential as getting a safe and potent CBD product from a reliable supplier may prove challenging.
Given that the studies on CBD interactions with antidepressants are limited, it is not easy to conclude what can potentially happen when a dose of CBD is taken with antidepressants like Zoloft.
Discontinuing Zoloft use without the advice of a doctor is not recommended. The best course of action is still to consult with a medical professional before considering CBD as one of the treatment options for depression and starting a CBD regimen.
Does CBD Interact With Sertraline (Zoloft)?
Information on risks & possible interactions between CBD & sertraline.
Zoloft, or sertraline, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It’s used in treating depression, panic attacks, obsessive-compulsive disorder, post-traumatic stress disorder, and premenstrual dysphoric disorder.
Cannabidiol or CBD has been gaining attention for its positive effects on anxiety, insomnia, inflammation, and depression.
Studies are still underway, though, and not much is known about the many other effects it could cause. CBD decreases particular enzymes’ abilities to metabolize Zoloft, so using them together could worsen the latter’s effects; however, the research is limited.
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Does CBD Interact With Sertraline?
CBD may act as a competitive inhibitor for the same enzymes that metabolize sertraline (Zoloft). It can prevent the actions of cytochrome P450 enzymes, the same enzymes that metabolize sertraline; theoretically, using them together could decrease sertraline’s metabolization and, thus, increase its effects.
Because of this, sertraline might remain in the body for longer and could cause some side effects, ranging from simple ones to serious ones, such as serotonin syndrome.
However, there are not enough studies to determine exactly how much of an effect there will be by using sertraline and CBD together.
Other Names For Sertraline
Sertraline is sold under many different names. All share the same risk and potential interactions.
Other names for sertraline include:
Similar Medications: CBD & SSRIs
Sertraline is classified as an SSRI (selective serotonin reuptake inhibitor). CBD and SSRIs all share similar risks for interaction and side effects.
Here’s a list of similar medications that share a similar level of risk when combined with CBD:
- Citalopram (Cipramil & Celexa)
- Dapoxetine (Priligy)
- Escitalopram (Cipralex & Lexapro)
- Fluoxetine (Prozac, Rapiflux, Sarafem, Selfemra & Oxactin)
- Fluvoxamine (Faverin)
- Paroxetine (Seroxat)
- Vortioxetine (Brintellix)
Is It Safe to Take CBD & Sertraline Together?
Because of CBD’s effects on the enzymes that metabolize sertraline (Zoloft), the latter drug is likely to be more potent than usual. This could lead to side effects and, at worst, may cause excessive serotonin levels, leading to symptoms similar to serotonin syndrome.
There’s not much information on the side effects of mixing these two drugs, but be on the safe side and exercise extreme caution.
If you want to mix CBD with sertraline (Zoloft), talk to your doctor first.
Is CBD a Viable Alternative to Sertraline?
Because CBD lacks extensive studies on its effectiveness, it cannot be considered a good alternative to sertraline (Zoloft). For now, it’s best to continue your regular dosage of Zoloft and talk to your doctor.
Under the advice of your medical practitioner, you may take both medications, but if you experience any abnormal symptoms, immediately stop CBD and contact your doctor.
What Is Sertraline (Zoloft)?
Sertraline hydrochloride was invented and marketed by Pfizer with the brand name Zoloft. It was approved for use by the FDA in 1999.
Sertraline is metabolized in the liver by several cytochrome enzymes, including CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP2D6.
|Other Names (other generics)||Lustral, Setrona, Zosert, Certrafine, Psyline, Sertima|
|CYP Metabolism||CYP2B6, CYP2C19, CYP2C9, CYP3A4, and CYP2D6|
|Interaction With CBD||Metabolic Competitor|
|Risk of Interaction||Moderate; patient needs careful monitoring|
What Does Sertraline (Zoloft) Do?
Sertraline (Zoloft) is an SSRI and inhibits the reuptake of serotonin in the brain.
Zoloft is used in treating depression, panic attacks, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder. Zoloft can also improve mood and sleep and make the patient feel a better sense of well-being.
Depression is a mental disorder characterized by persistent low mood and lack of interest in activities that the person had previously enjoyed. In most patients with depression, serotonin levels are deficient.
Serotonin is the hormone that stabilizes mood, feelings of happiness, and well-being. Its level decreases in conditions such as depression.
Sertraline binds to the serotonin transporter (SERT) and inhibits the CNS neuronal retaking of serotonin (5HT). It prevents the fast metabolism of serotonin, thus allowing it to last longer in the brain, long enough for the person to function well again.
Side Effects of Sertraline
Like most other medications, sertraline (Zoloft) also has side effects. It affects the body as a whole and not just one system. These side effects usually happen on overdosing or incorrect dosing of the medication.
Side Effects In More Than 10% of Patients:
- Ejaculation disorder
- Dry mouth
Side Effects In Less Than 10% of Patients:
Rare Side Effects:
- Back pain
- Chest pain
- Increased appetite
- Weight gain
Possible Complications With Sertraline
There are some things about sertraline (Zoloft) that one should know before taking it. In some instances, Zoloft can be more dangerous. Here are a few situations:
1. Monoamine Oxidase Inhibitors (MAOI)
It can interact with MAOIs causing a decrease in serotonin metabolism, leading to an increased serotonin level, called Serotonin Syndrome. Its symptoms are high blood pressure, rapid heart rate, nausea, vomiting, and anxiety, and can be dangerous.
The oral solution of sertraline contains alcohol, so using them together can cause flushing, headaches, nausea, and vomiting.
3. Liver & Kidney Impairment
Patients with liver and kidney problems cannot properly remove sertraline from the body; low doses under supervision are required.
Using sertraline during pregnancy can cause congenital heart defects in the newborn.
Breastfeeding mothers with depression can use sertraline since its appearance in breast milk is minimal.
6. Patients Under 25
One of sertraline’s significant side effects is an increased risk of suicide in people under 25 years. This age group requires constant monitoring.
What Is CBD?
CBD, or cannabidiol, is a compound extracted from cannabis, usually hemp, to comply with federal law. It’s the second most common cannabinoid in cannabis, making up almost 40% of it.
There are many ways to take CBD, including inhalation, orally, or topically — topical application only works on the area it’s applied to. It does not cause alterations in mood or intoxication like another popular cannabinoid, delta-9 tetrahydrocannabinol (THC).
CBD has been the topic of many studies over the past few decades. It’s useful in treating anxiety, cognition, movement disorders, and pain.
In 2018, a cannabidiol drug, Epidiolex, was approved by the FDA. Epidiolex is used for the treatment of two rare epilepsy conditions. In some parts of the world, CBD combined with THC in a 1:1 combination is approved for use in symptomatic relief for adults with Multiple Sclerosis.
What Does CBD Do?
CBD interacts with the endocannabinoid system (ECS); this complex system is found throughout the body and is composed of endocannabinoids, enzymes, and cannabinoid receptors.
There are two receptors of most importance in the ECS, called CB1 and CB2. CB1 is associated with the nervous system, while CB2 is found mainly in the immune system.
THC binds directly to the CB1 and CB2 receptors. CBD, however, alters the behavior of the receptors, causing a reaction.
CBD can activate 5-HT1A/2A/3A serotonergic receptors. While it doesn’t necessarily increase serotonin levels in the brain, it may affect the chemical receptors’ response to the already available serotonin .
CBD is metabolized in the liver by several cytochrome P450 enzymes and acts as a competitive inhibitor for these same enzymes. It occupies sites of enzymatic activity and displaces its chemical competitors. Due to this, these enzymes of cytochrome P450 are unable to metabolize other compounds.
CBD may have a benefit over other medications used in depression. While antidepressants take a few weeks to start working, CBD can show antidepressant-like effects much sooner.
CBD does not have side effects like most antidepressants do. There are no side effects like insomnia, sexual dysfunction, or mood swings with CBD .
Side Effects of CBD
- Potential liver damage
- Decrease in blood pressure
Important Points To Consider About CBD
You need to know a few things about CBD that may impact how you buy and use it.
The FDA Does Not Regulate CBD
Two drugs, Epidiolex and Sativex, contain CBD and have received approval for use.
CBD and CBD products are largely unregulated and are not FDA-approved. Unfortunately, this leaves a large gap, and the quality and safety of these products are often called into question. There are many good companies, but you have to watch out for the bad ones.
Often, companies lie about the amount of CBD in the products or add chemicals to make them seem more potent.
Even though many studies find CBD to be beneficial, the research is still lacking. We don’t know the full extent of its abilities and side effects yet, especially long-term.
Types of Drug Interactions With CBD
There are three different ways that CBD can interact with other drugs.
1. Agonistic Interaction (Increased Effect)
This happens when two substances have the same effects in the body due to both of them acting on the same receptors to push in the same direction.
These include drugs like:
- Antihypertensive medications — ACE inhibitors, alpha-blockers, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, central agonists, and diuretics.
- Anti-anxiety medications — Benzodiazepines and barbiturates.
- Antidiabetic medications — Alpha-glucosidase inhibitors, biguanides, DPP-4 inhibitors, GLP-1 receptor agonists, meglitinides, SGLT-2 inhibitors, sulfonylureas, and insulin.
Antagonistic Interaction (Decreased Effect)
This decreases the effects of the medication.
These include medications like:
- Stimulants — Amphetamine, modafinil
- Immunomodulators — Antihistamines like carbinoxamine, desloratadine, levocetirizine
- Immunosuppressants — Azathioprine, mycophenolate cyclosporine, methotrexate
These medications need similar enzymes to break down the drug molecules, causing both types of medications to compete against each other, leading to a slow metabolism rate for both of them. They may increase the effects or decrease the effects.
These include medications like:
- Blood Thinners — Enoxaparin, heparins, and others
- NSAIDs — Ibuprofen, naproxen, high-dose asprin
- Opiate analgesics — Morphine, codeine, hydrocodone
- Antidepressants — Trazodone, mirtazapine, vortioxetine, and vilazodone
Key Takeaways: Is it Safe to Take Sertraline (Zoloft) With CBD?
While theoretically, taking sertraline with CBD could cause some serious side effects, the studies are still limited. It’s better to exercise caution and talk with your doctor before you use CBD with sertraline. If you feel any side effects on using these drugs together, seek medical attention immediately.