Updated on February 6, 2024
8 min read

Zoloft and Weed: Can You Take Them Together?

Since Zoloft (sertraline) received FDA approval in 1999, doctors have been prescribing it to relieve symptoms of anxiety and depression.1 Moreover, more Americans are using weed (marijuana) for medicinal or recreational use.

With the use of both Zoloft and marijuana rising in recent years, health experts are now looking into the dangers of concurrently using antidepressants (like Zoloft) and marijuana, including the delta-8 THC variant.

Can You Mix Zoloft and Weed?

Using Zoloft and weed simultaneously is not recommended. Combining these two can result in various drug interactions that adversely affect the mind and body, such as: 

Amplified Side Effects

The few studies on the drug interactions between Zoloft and weed suggest that using both may increase the risk and severity of each substance’s side effects. One factor is marijuana’s ability to inhibit liver enzymes needed to metabolize Zoloft.

When the body can’t process and remove Zoloft fast enough, it could lead to higher-than-normal levels of Zoloft in the bloodstream. This increases Zoloft’s adverse reactions.10,13,14

Using the two drugs simultaneously may also amplify their sedative effects, leading to excessive sleepiness and impaired thinking.15

Excessive Serotonin Levels

Serotonin syndrome is a rare but potentially life-threatening condition caused by excessive serotonin levels. Both Zoloft and marijuana can boost serotonin to dangerously high levels, which can increase the risk of developing this condition.

Some symptoms that characterize serotonin syndrome include:3

  • Shivering
  • Diarrhea
  • Confusion
  • Severe muscle tightness
  • Fever
  • Seizures
  • Death

Compromised Mental Health

Marijuana’s impact on a person’s mental health can be unpredictable. This is due to the marijuana’s varying THC/CBD ratio that depends on the marijuana’s strain, purity, dosage, and frequency of use.6,16

At higher doses, smoking weed can cause psychosis and severe mood disorders. Mixing Zoloft and weed can also exacerbate depression, anxiety, panic attacks, and OCD, conditions that Zoloft is supposed to address.5,10

Moreover, marijuana may mask Zoloft’s treatment effectiveness. When people take Zoloft and weed simultaneously, they might stop taking the antidepressant medication because they think it’s not working. This could worsen their condition by skipping their prescribed treatment.5

Zoloft and Delta-8 THC: A Special Consideration

Delta-8 THC is milder and has a lower cannabis concentration than delta-9 THC, but it still presents concerns about its use:6,7,8

  • There are several reports of delta-8 THC's adverse reactions, like poisoning and even death.
  • Solvents and other chemicals can contaminate delta-8 THC during manufacturing. Manufacturers synthesize delta-8 THC from hemp-derived CBD since it is in small amounts in cannabis.
  • The combination of Zoloft and delta-8 THC has similar concerns with the combination of Zoloft and delta-9 THC. This is due to delta-8 THC having psychoactive, intoxicating, and serotonin-boosting effects, even at lower cannabis concentrations. 

Whether you’re considering using Zoloft with delta-8 THC or delta-9 THC, it’s vital to consult a healthcare professional before doing so. They must assess your medical history, current medications, and mental health condition to determine the safety of combining these substances.


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Is it Safe to Mix CBD and Antidepressants?

It would be best to exercise caution when combining CBD with Zoloft or any antidepressant medication without consulting a healthcare professional. While CBD is considered safe due to being therapeutic and non-psychoactive, it can still interact with Zoloft and other antidepressants.17,18

  • CBD shares some side effects with several antidepressants (like nausea and drowsiness). Taking CBD and antidepressants together can exacerbate these effects. 
  • CBD may compete for or interfere with liver enzymes. This action can alter the level of antidepressants in the body and increase their side effects.

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What is Zoloft?

Zoloft, also known as sertraline, is an antidepressant that belongs to a group of medications called selective serotonin reuptake inhibitors (SSRIs). These drugs inhibit serotonin's reuptake (reabsorption), a neurotransmitter that regulates mood and emotions.

What is Zoloft For?

The FDA approved the use of Zoloft for the treatment of the following conditions:1,2

  • Major depressive disorder (MDD)
  • Post-traumatic stress disorder (PTSD)
  • Premenstrual dysphoric disorder (PMDD)
  • Panic disorder (PD)
  • Social anxiety disorder (SAD)
  • Obsessive-compulsive disorder (OCD)

It’s also prescribed off-label for the treatment of:2

  • Binge-eating disorder
  • Bulimia nervosa
  • Generalized anxiety disorder (GAD)

What are the Potential Side Effects of Zoloft?

Some people taking Zoloft may experience common side effects, including:1,2,3,4

  • Nausea
  • Headaches
  • Insomnia or difficulty staying asleep
  • Diarrhea
  • Constipation
  • Vomiting
  • Dry mouth
  • Excessive tiredness or weakness
  • Heartburn
  • Loss of appetite
  • Weight changes
  • Dizziness
  • Drowsiness
  • Nervousness
  • Uncontrollable shaking of a part of the body
  • Increased sweating
  • Sexual problems (like decreased sex drive, delayed orgasm, or inability to get or maintain an erection)

Understanding Weed: The Different Components, Types, and Their Effects

Derivatives of the cannabis plant can be turned into psychoactive drugs that come from a mixture of the plant’s dried flowers, leaves, seeds, and stems.

Marijuana can be packaged and processed into different types, such as:

  • Weed
  • Marijuana
  • Pot
  • THC
  • CBD

They contain chemicals known as cannabinoids, with THC and CBD as the most notable for their psychoactive effects.

Smoking marijuana was the most prominent method of experiencing cannabis, but more modern products allow marijuana to be mixed in food, ingested through vape cartridges and applied through topical creams.

CBD (Cannabidiol)

CBD is another prominent cannabinoid found in cannabis. It’s non-psychoactive and more known for its potential therapeutic benefits, such as:6

  • Pain relief
  • Anti-anxiety effects
  • Anti-inflammatory properties

THC (Tetrahydrocannabinol)

THC is responsible for marijuana’s euphoric and intoxicating effects. The two popularly known THCs are:6,7,8

  • Delta-9 THC: This is marijuana’s primary psychoactive compound extracted directly from the marijuana plant. It produces the well-known "high" associated with marijuana use. 
  • Delta-8 THC: Structurally similar to delta-9 THC, this compound has a milder psychoactive effect. It’s manufactured from hemp-derived CBD, making it legal in many states since it has much lower concentrations of THC.

Common Cannabis Strains

Cannabis has over 700 strains, with these three as the most prominent:9

  • Cannabis indica: Indica strains typically have higher CBD levels and lower THC levels. People usually choose indica strains to relieve anxiety, stress, and insomnia.
  • Cannabis sativa: Sativa strains tend to have higher THC and lower CBD levels, which characterize their euphoric and intoxicating effects.
  • Cannabis ruderalis: This strain is less common than indica and sativa strains and usually has the lowest THC levels. People often use ruderalis strains to crossbreed and create hybrid cannabis variants.

How Does Weed Interact with the Brain?

Weed interacts with the brain through its active cannabinoids (primarily delta-9 THC and CBD) by engaging with the brain’s endocannabinoid system (ECS).6,10,11 

The ECS is a complex network of receptors and neurotransmitters in the brain and nervous system. It consists of two main types of receptors:

  • CB1 receptors: Primarily located in the brain and central nervous system
  • CB2 receptors: Found in the peripheral organs and immune cells.

Interaction with CB1 receptors causes marijuana’s psychoactive effects, while CBD’s impact on other receptors may explain its potential therapeutic benefits.

Common Side Effects of Marijuana

Using marijuana comes with side effects, including:5,12

  • Tachycardia (rapid heartbeat)
  • Changes in blood pressure
  • Dizziness
  • Drowsiness
  • Nausea
  • Vomiting
  • Abdominal pain
  • Breathing problems
  • Increased coughing or mucus production
  • Short-term impairment in learning, memory, and attention
  • Tiredness
  • Changes/Increases in appetite (the munchies)

Depending on the grade and type of weed smoked, the experienced adverse reactions could be minimal or severe. In some cases, the user would need emergency medical attention. 

What Substances Interact with Zoloft?

Apart from cannabis, other substances, medications, and supplements can have adverse interactions with Zoloft. Here are a few examples:1,2,19

  • Monoamine oxidase inhibitors (MAOIs): Mixing Zoloft with MAOIs can lead to serotonin syndrome. MAOIs are another class of antidepressants.
  • Other serotonin-boosting drugs and supplements: Mixing Zoloft with other SSRIs (like Prozac and Paxil) or SNRIs (like Effexor and Cymbalta) may also increase the risk of serotonin syndrome. Combination with tricyclic antidepressants (TCAs) and the herbal supplement St. John’s Wort can produce the same result.
  • Alcohol: Alcohol can increase the sedative effects of Zoloft and impair cognitive function. It may also worsen depressive symptoms.
  • Anticoagulants: Zoloft can interact with certain anticoagulants or blood thinners (such as warfarin), leading to an increased risk of bleeding.
  • Drowsy medications: Combining Zoloft with some antihistamines and sedative medicines can further intensify drowsiness.

This is not an exhaustive list. Tell your doctor about your current medications and supplements before taking Zoloft. 

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Weed, marijuana, pot, or cannabis contains various compounds, primarily THC and CBD, that affect brain chemistry. Products like Delta 9, derived from THC, are illegal according to federal statutes, while Delta 8 products manufactured from CBD/hemp are not restricted at the federal level.

Antidepressants, like Zoloft, also influence brain chemistry as its treatment mechanism. The effects that Zoloft and weed have on the brain and body can go in different ways, so combining the two substances is not a good idea. Both could increase the risk of side effects, cause excessive serotonin levels, and worsen depression or anxiety disorders. 

Regardless if you’re using recreational or medical marijuana, it’s essential to have discussions with your doctor. They may not prescribe Zoloft if you’re using marijuana or advise against CBD products if you’re undergoing Zoloft treatment to prevent potential drug interactions.

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Updated on February 6, 2024
19 sources cited
Updated on February 6, 2024
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  3. Side effects - Selective serotonin reuptake inhibitors (SSRIs).” NHS, 2021.
  4. Sertraline.” Medline, 2022.
  5. Cannabis (Marijuana) DrugFacts.” National Institute on Drug Abuse (NIDA), 2019.
  6. Alsherbiny, M.A.,  and Li, C.G. “Medicinal Cannabis-Potential Drug Interactions.” Medicines (Basel), 2019.
  7. 5 Things to Know about Delta-8 Tetrahydrocannabinol – Delta-8 THC.” U.S. Food and Drug Administration (FDA), 2022.
  8. Rae, A., and Woodcock, S. “What Is Delta-8 THC, and Is It Safe?” GoodRx Health, 2023.
  9. Gloss, D. “An Overview of Products and Bias in Research.” Neurotherapeutics, 2015.
  10. Vaughn et al. “The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.” Journal of Personalized Medicine, 2021.
  11. How does marijuana produce its effects?” National Institute on Drug Abuse (NIDA), 2020.
  12. What are the side effects of marijuana?” Drugs.com. 2022.
  13. Nasrin et al. “Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions.” Drug Metabolism and Disposition, 2021.
  14. Anderson et al. “Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People.” Journal of Clinical Psychopharmacology, 2021.
  15. Drug Interactions between cannabis and Zoloft.” Drugs.com.
  16. Scherma et al. “New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders.” Medicines (Basel), 2018.
  17. Bykov, K. “CBD and other medications: Proceed with caution.” Harvard Health Publishing, 2021.
  18. Drug Interactions between cannabidiol and Zoloft.” Drugs.com.
  19. Ulrich, A. “7 Sertraline Interactions to Watch For.” GoodRx Health, 2023.

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