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What Happens When You Mix Zoloft and Weed?

zoloft and weed grapefruit and cannabis
Is it safe to use Zoloft and weed?

Cannabis as Medicine

Cannabis is being used to treat a variety of health issues, from PTSD to Alzheimer’s disease to chronic pain to inflammation to cancer to migraines to concussive traumatic encephalopathy (CTE).

For most patients, marijuana is safer than other pharmaceuticals.

Still, it’s important to note, in some patients, marijuana can and does affect the absorption rates of some prescription medications.  Much in the same way that grapefruit juice does.

Cannabis can interact with prescription medications by utilizing the metabolic pathway Cytochrome P450 in the liver & intestines.

Can Zoloft Interact With Marijuana?

Although rare, drug interactions are possible with Zoloft and marijuana.

Patients taking Zoloft (or other antidepressants) should use caution with cannabis.

Could Cannabis Be as Dangerous as Grapefruit?

Drug interactions are rare, but in theory, marijuana may be as dangerous as grapefruit.

(Note:  Patients many prescription medications should also use caution with grapefruit.)

Patients are frequently warned about consuming grapefruit with some medications. The metabolism of some cannabinoids is similar to grapefruit.

What happens when you combine antidepressants and marijuana?

Mixing Zoloft and weed can result in a higher amount of Zoloft in your blood (so can mixing Zoloft and grapefruit juice).   This is essentially equivalent to taking a higher dose of medication.

Does It Increase the Risk of Side-Effects?

Higher levels of medication can increase the risk of experiencing negative side-effects.

Most patients don’t experience a noticeable interaction, however, there are plenty of anecdotal reports of negative side effects from combining Zoloft and marijuana.

Reported symptoms include severe panic attacks.

No interactions have been observed in a clinical setting, but patients report temporary symptoms that eventually subside.  This interaction can be a scary experience for the patient.

Also, keep in mind that smoking weed vs eating edibles can produce a different physiological experience.

If you’re making edibles, try these single serving edibles, first.

Mixing Zoloft and weed occasionally results in an adverse reaction.

What Patients Should Know About Mixing Zoloft with Marijuana

No Clinical Evidence, But Some Reports

There is NO research or clinical evidence that a drug interaction with marijuana can be deadly. However, caution should be utilized.

It needs to be noted that high levels of Zoloft in the blood can cause serotonin syndrome.  Serotonin syndrome is a side effect of many antidepressants and is easily treated. However, it can be fatal when left untreated.

What If You Mix Cannabis And Anti-Depressants?

If you’re a patient on antidepressants, learn about the side effects of your prescription medication. Understand, that reactions between cannabis and antidepressants have been reported.

Talk to your doctor about your marijuana status (you may require a lower dose of antidepressants).

Marijuana might be as dangerous as grapefruit, but it’s not as deadly as alcohol or nutmeg (seriously, nutmeg is potentially deadly!)

 READ:  25+ Unique Marijuana Pipes on Amazon.


How Grapefruit Affects Prescription Medication

It’s not uncommon to see a warning on a prescription bottle instructing the patient to avoid grapefruit juice while taking a medication.

Nurses commonly guide warfarin patients to avoid sudden changes in the amount of leafy greens they consume.  And doctors profess that mixing alcohol with painkillers can be fatal.

Asking about marijuana and drug interactions is smart.

Different foods, drinks, and chemicals we put into our body can change the way our body works.  So if drinking grapefruit juice can be fatal with some medications, what about weed? Can marijuana affect prescription medications?

Of course, it’s possible.

zoloft and weed - Can marijuana interact with prescription medication?

READ:  Recipe for ABV Coconut Oil


How Cytochrome P450 Metabolism Works

Imagine your body is a cherry tree.

Imagine for a moment that the Zoloft molecules are cherries.  You take a Zoloft pill, it splits into thousands of cherries and they start floating around in your blood.


Cytochrome P450

Well, your liver and intestines have special “cherry pickers”.  These cherry pickers are called Cytochrome P450.  Cytochrome P450’s job is to collect the cherries and convert them into something the body can use & dispose of.

But in order for a medication like Zoloft (and lots of other antidepressants) to be effective, the proper levels of medication need to accumulate at a specific concentration in the blood.  Once the medication reaches the ideal concentration, the patients will see desired effects.

This is why doctors say it takes 4-8 weeks to notice a difference when beginning antidepressants.  Ideal levels of Zoloft take time to build up in the blood.


If you’re gift shopping check out these 50+ Stoner Gifts For Under $20.


When Zoloft reaches the ideal level, the patient feels better (in theory).

As our CYP450 cherry pickers work as hard as they can, the balance of the cherries accumulates in our blood.  When there are enough cherries in our blood, the medicine boosts serotonin levels in the brain which makes the patient feels better.

Medications like Zoloft need a constant & consistent level within the blood in order to work effectively.

cherries drug interactions mmj

The Challenge of Zoloft and Weed

The challenge arises when combinging some antidepressants, like Zoloft and weed because they both use the same “cherry pickers”.

Mara Gordon, founder of Zelda Therapeutics, explains, “the active components of medical marijuana, CBD especially, and to a lesser extent THC” also utilize pathway CYP450.

So, in some patients when they mix Zoloft and weed, the Zoloft molecules are not the only kind of cherry anymore. All of these molecules compete for the same cherry pickers.

Read:  Project CBD – CBD Drug Interactions 

So when you add weed and Zoloft together, you get a sudden influx of cherries in the blood!  Yet, you have the same limited number of CYP450 cherry pickers.


Too Many Cherries

Cherry pickers can only work so hard and you’re already at a max.

In the end, the patient’s blood becomes inundated with unpicked cherries  – many more cherries than your doctor had planned.

This means the blood level of the medication increases.  This could be the equivalent of taking a higher dose of Zoloft than intended.  This also means the blood levels of cannabinoids will be higher than expected.

Because antidepressants need consistency to function properly – taking both Zoloft and weed should be monitored by a doctor.


Marijuana & Drug Interactions Can Vary Person to Person


In different people and different populations, activity of CYP oxidases differs. Genetic variation in a population is termed ‘polymorphism’ when both gene variants exist with a frequency of at least one percent. Such differences in activity may have profound clinical consequences, especially when multiple drugs are given to a patient. There are profound racial differences in the distribution of various alleles – data on a drug that works in one way in one population group cannot necessarily be extrapolated to another group.


Basically, that means that my cytochrome P450 cherry pickers don’t look or behave the same way as your CYP450 cherry pickers. Also, our cherry pickers might not move at the same speeds. These individual differences make predicting drug interactions difficult.


Gene Expressions Differ Causing Different Risks

According to this 2011 research study, the most important CYP450 isoforms metabolizing CBD are CYP3A4 and CYP2C19.  This 2005 study shows that Zoloft also utilizes CP2C19. According to, CYP2C19 is polymorphic.  Different expressions of CYP2C19 may explain why some patients report negative side effects when taking Zoloft and weed.


Can An Interaction Be Deadly?

Internet stories abound, detailing patients’ scary experiences after combining anti-depressants and weed. Many of these users describe what sounds like severe panic attacks.  Panic attacks are a possible side-effect of both Zoloft and marijuana.


NO Evidence of Fatal Reactions

Again – There is NO research or clinical evidence that a drug interaction with marijuana can be deadly. However, caution should still be utilized.

High levels of Zoloft in the blood can cause serotonin syndrome, a potentially fatal (but easily treated) side effect of many antidepressants.


Conclusion: Should I stop smoking weed?

That’s a personal question only you can answer.

Is your life at risk?  Most likely no, many people function perfectly well taking both antidepressants and marijuana. Most patients never report negative experiences.

Still, our research into cannabis is limited.  We expect to uncover more about risks and side-effects as we explore this new branch of medicine.  Until then please research and understand the side-effects of your prescription medication and use cannabis cautiously.


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Written by Jessie Gill

Jessie Gill, RN is a cannabis nurse with a background in holistic health and hospice. After suffering a spinal injury, she reluctantly became a medical marijuana patient then quickly transitioned into an advocate. Her site, combines science with personal insight to educate about medical marijuana. She’s been featured on Viceland and bylines include GoodHousekeeping, Cosmopolitan, MSN, and more.

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