What Are the Risks of Combining Vyvanse and Zoloft with Weed?

In our latest question and answer our pharmacist discusses the risk of combining vyvanse, zoloft, and weed.
What Are the Risks of Combining Vyvanse and Zoloft with Weed?

Rachel Asked

My therapist told me I have to take a drug test for weed because I’m on vivavans and Zoloft. She said new studies show it’s not safe to take with weed. Is this true? Any loopholes to avoid this? Like a medical card?


Vyvanse (lisdexamfetamine) is a long-acting stimulant drug used to treat symptoms of ADHD and binge-eating disorder.
Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI) medication used to treat various mental disorders (depression for example).
Cannabis can increase the concentrations of certain SSRIs, possibly increasing the risk for serotonin syndrome but more research is needed.
Doctors who prescribe controlled substances, like Vyvanse, like to monitor that you're actually taking the drug.


Thanks for the question, Rachel. While there's not any new research I'm personally aware of, there is some cause for concern with this combination which I'll outline below.

What are The Risks of Using Weed While Taking Vyvanse  and Zoloft?

1. Increased risk of side effects:

  • Cannabis might inhibit liver enzymes that metabolize zoloft. This could theoretically lead to higher levels of Zoloft in the blood and increase the risk of side effects like nausea, dizziness, and something called serotonin syndrome. See below for more about serotonin syndrome. 
  • The stimulant effects of Vyvanse combined with the depressant effects of marijuana can lead to unpredictable reactions and potential cardiovascular issues. 

2. Increase risk of serotonin syndrome:

  • Serotonin syndrome is a serious adverse drug reaction. It can occur when patients are prescribed multiple drugs that cause levels of serotonin in the body to rise. Serotonin is a natural chemical produced by the body and is needed for normal brain and nervous system function, but too much of it can cause issues like shivering, diarrhea, muscle rigidity, fevers, and seizures. 
  • Stimulants like Vyvanse cause an increase in the availability of serotonin and inhibit its reuptake. SSRIs, like Zoloft, also inhibit reuptake of serotonin (hence their name "Selective Serotonin Reuptake Inhibitors"). Cannabis may stimulate serotonin receptors and has been associated with case reports of serotonin syndrome. So while Vyvanse and Zoloft already increase the risk of serotonin syndrome, cannabis may further increase that risk. 

3. Impaired effectiveness:

  • Cannabis has complex effects on the brain. While it's not known for sure, cannabis use could counteract or diminish the intended therapeutic effects of Zoloft and Vyvanse, potentially worsening the symptoms that these medications are meant to treat! For instance, cannabis may cause problems with cognition and attention which can already be impaired in conditions like depression and ADHD. 

4. Increased risk of psychological and cardiac effects:

  • Cannabis has been associated with dysphoric reactions in some individuals. These reactions are usually characterized by anxiety, panic-like symptoms, and paranoia. Stimulants like vyvanse have been associated with adverse psychological effects. 
  • Cannabis and stimulants both increase heart rate and blood pressure, increasing demand on the heart. This likely explains why both drugs have been associated with increases in cardiac events

While not necessarily life-threatening on their own, the combination of these substances can lead to serious complications and undermine the treatment of the underlying conditions (specifically those that necessitate your treatment with zoloft and vyvanse. Most experts would advise against combining these medications with marijuana due to the potential risks and interactions. However, that doesn't mean the combination is completely unsafe. 

Can This Combination Be Used Safely?

Yes, but due to the risks outlined above, I'd recommend being open and honest with your doctor about your cannabis use. Cannabis is legal for adults almost everywhere in the US, so it's not like you're doing anything wrong as long as you are of legal age. Familiarize yourself with the signs and symptoms of serotonin syndrome and be sure to seek medical care if they occur. 

Signs and Symptoms of Serotonin Syndrome

  • Serotonin syndrome and cannabis: A case report
    Agitation or restlessness
  • Insomnia
  • Confusion
  • Rapid heart rate and high blood pressure
  • Dilated pupils
  • Loss of muscle coordination or twitching muscles
  • High blood pressure
  • Muscle rigidity
  • Heavy sweating
  • Diarrhea
  • Headache
  • Shivering
  • Goose bumps

What Can I Do About the Test? Will Getting My Medical Card Help?

Doctors prescribing controlled substances, like vyvanse, often order drug tests to monitor therapy and for abuse/misuse. By ordering a drug test they can make sure that you're actually taking the drug they're prescribing and not selling it on the street. They can also check if you're abusing other illegal or prescription drugs which would raise concern that you might also be doing that with Vyvanse. 

I'd just be open and honest with your doctor about your cannabis use. It is legal as long as you are above the age of 21. If they truly are worried about cannabis interacting with your medications tell them how it's been going so far. As long as your medications have been working properly and there aren't any side effects you find concerning they might be fine with it. I think honesty is the best policy in this case. It might also be a good idea to ask about the research they referenced previously so that you can learn more about what to look out for. 

I don't think getting a medical card will help in this circumstance because your doctor might not care if your cannabis use is recreational or medical in nature. I could be wrong though! 

I hope this helps!

  1. Serotonin syndrome and cannabis: A case report (PubMed).
  2. Association of Cannabis Use With Cardiovascular Outcomes Among US Adults (Article).

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