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Research

Serotonin Syndrome Unmasked: Can Cannabis and Psychedelics Trigger This Mysterious Condition?

Lemetria Whitehurst

by Lemetria Whitehurst

April 22, 2024 08:00 am ET Estimated Read Time: 8 Minutes
Fact checked by Kymberly Drapcho Medically reviewed by Dr. Carlie Bell
Serotonin Syndrome Unmasked: Can Cannabis and Psychedelics Trigger This Mysterious Condition?

It’s become increasingly common to hear stories of those suffering from serotonin syndrome, but for some, the full scope and depth of this mysterious condition remain shrouded in mystery. Are psychedelic drugs and cannabis capable of triggering this serious medical issue? In this post, we’ll dive into what serotonin syndrome is, how you may be able to identify it, and whether or not these substances can play a role in its development.

What Is Serotonin Syndrome?

Serotonin syndrome is a potentially life-threatening disorder caused by too much serotonin in the body. This can happen when someone takes multiple serotonin-boosting medications or consumes too much of a single medication. Serotonin syndrome can cause the following symptoms:

  • Agitation
  • Confusion
  • Muscle rigidity
  • Rapid heart rate
  • High blood pressure 
  • Death (if left untreated)

While it may sound bizarre and rare, it is a real possibility, especially among individuals who take antidepressants. It’s essential to recognize serotonin syndrome symptoms early on and seek medical attention immediately. 

Which Medications Put a Person at High Risk of Developing Serotonin Syndrome?

Certain medications that affect serotonin levels can put a person at a higher risk of developing serotonin syndrome, particularly when used in combination with other similar drugs or at high doses. Some of these medications include:

  • Selective serotonin reuptake inhibitors (SSRIs): A common class of antidepressants, which include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and citalopram (Celexa)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs): Another class of antidepressants, such as venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq)
  • Tricyclic antidepressants (TCAs): Older generation antidepressants like amitriptyline (Elavil), nortriptyline (Pamelor), and imipramine (Tofranil)
  • Monoamine oxidase inhibitors (MAOIs): A less commonly used class of antidepressants, including phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan)
  • Serotonin modulators: Medications such as trazodone (Desyrel) and vilazodone (Viibryd)
  • Triptans: Migraine medications like sumatriptan (Imitrex), rizatriptan (Maxalt), and zolmitriptan (Zomig)
  • Pain medications: Certain opioids like tramadol (Ultram), meperidine (Demerol), and fentanyl (Duragesic)
  • Herbal supplements: St. John’s Wort and some dietary supplements like L-tryptophan and 5-HTP, which raise serotonin levels
  • Parkinson’s disease medications: Medications such as carbidopa-levodopa (Sinemet) and selegiline (Eldepryl, Zelapar)
  • Illicit drugs: Substances such as cocaine, amphetamines, and MDMA (ecstasy), which can also elevate serotonin levels and contribute to the risk of developing serotonin syndrome


It’s important to note that the risk of serotonin syndrome increases if two or more serotonergic medications are taken together or in close proximity. If you are concerned about the possibility of serotonin syndrome, consult your healthcare provider before starting, stopping, or adjusting the dosage of any medications or supplements. They can help you understand the potential interactions and suggest alternative options.

The Role of Cannabis in Serotonin Syndrome

As the use of cannabis becomes increasingly prevalent, it’s essential to understand the potential impact of cannabinoids on serotonin syndrome. Let’s begin by exploring the endocannabinoid system, which plays a crucial role in regulating various physiological processes, including mood, pain sensation, and immune response. Cannabis, through its active compounds like THC and CBD, interacts with this system, influencing the release of neurotransmitters such as serotonin.

While research on the direct effects of cannabis on serotonin levels is still in its infancy, some studies and anecdotal evidence suggest a possible connection between cannabis use and serotonin syndrome. However, it’s worth noting that most reported cases involve using cannabis with other serotonergic medications or substances. This highlights the potential for drug interactions and the importance of exercising caution when using cannabis alongside other medicines.

The Role of Psychedelics in Serotonin Syndrome

The world of psychedelics is vast and multifaceted, with these mind-altering substances significantly influencing the serotonin system. The psychedelics drug class includes: 

  • LSD (lysergic acid diethylamide)
  • psilocybin (found in “magic mushrooms”)
  • DMT (dimethyltryptamine)
  • MDMA (3,4-methylenedioxymethamphetamine, also known as ecstasy or molly), 


These substances mainly function by imitating serotonin and attaching to its receptors within the brain. As a result, significant changes in perception, emotional state, and thought processes can occur.

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While psychedelics have contributed to a range of therapeutic benefits, it’s essential to consider the potential risks, such as the development of serotonin syndrome. Although rare, there have been case reports and research studies suggesting a connection between the use of psychedelics and serotonin syndrome. Like cannabis, this is more likely to occur, especially when these substances are used with serotonergic medications or other drugs with serotonin agonist effects.

How Is Serotonin Syndrome Diagnosed and Treated?

Since there isn’t a specific lab test to confirm serotonin syndrome, healthcare professionals rely on patient history, physical examination, and evaluating the presence of symptoms to make a diagnosis. The Hunter Serotonin Toxicity Criteria is a commonly used tool for identifying the condition based on clinical findings.

Once serotonin syndrome is suspected or diagnosed, prompt treatment is crucial. The primary course of action involves:

  • Discontinuing the causative agent(s): Stopping any medications or substances contributing to excessive serotonin levels is the first step. It’s essential to consult with a healthcare professional to determine the appropriate course of action.
  • Supportive care: Managing symptoms and ensuring patient stability is vital. This may include intravenous fluids to maintain hydration, oxygen therapy, or medications to alleviate agitation, high blood pressure, and muscle rigidity. In severe cases, sedatives or muscle relaxants may be administered.
  • Serotonin antagonists: In some instances, healthcare professionals may prescribe serotonin antagonists, such as cyproheptadine, to counteract the effects of excessive serotonin levels.
  • Close monitoring: Patients diagnosed with serotonin syndrome require close observation to ensure their symptoms resolve and don’t worsen. This may involve continuous monitoring of vital signs and neurological status.
  • Addressing complications: In severe cases, additional interventions may be needed to manage complications, such as seizures, respiratory failure, or kidney damage.

How to Prevent Serotonin Syndrome

When it comes to serotonin syndrome, an ounce of prevention is truly worth a pound of cure. You can effectively reduce the risk of this potentially life-threatening condition by staying vigilant and informed. Start by recognizing the risk factors, such as using multiple serotonergic medications or combining certain medications and substances like cannabis or psychedelics. Monitoring your substance use and being aware of potential interactions are key to avoiding complications.

Also, don’t hesitate to communicate openly with a healthcare professional about the medications, supplements, or substances you are using. They can guide you on safely adjusting dosages or suggest alternative options to minimize the chance of developing serotonin syndrome. 

If you suspect serotonin syndrome in yourself or someone else, seeking prompt medical attention is crucial. Early intervention can make a significant difference in managing the condition and preventing severe complications. By staying proactive and informed, you can safeguard yourself and others from the dangers associated with serotonin syndrome and promote a healthier, more balanced approach to health and wellness.

Final Thoughts

Without a doubt, this article offers a significant amount of detail about the dangers associated with serotonin syndrome, from what it is and how physicians diagnose it to cannabis and psychedelic roles. As previously mentioned, one can take many preventative measures when combining serotonergic medications with other substances.

To stay safe while exploring treatments with marijuana or psychedelics, don’t forget to consult with your primary care physician or pharmacist before mixing medications. This condition can be prevented and managed by increasing awareness and practicing responsible substance use.

Sources

  1. Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
  2. Artin, H., Zisook, S., & Ramanathan, D. (2021). How do serotonergic psychedelics treat depression: The potential role of neuroplasticity. World journal of psychiatry, 11(6), 201–214.
  3. Frank C. (2008). Recognition and treatment of serotonin syndrome. Canadian family physician Medecin de famille canadien, 54(7), 988–992.
  4. Nadeem, Z., Wu, C., Burke, S., & Parker, S. (2024). Serotonin syndrome and cannabis: A case report. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 32(1), 100–101.
  5. Carhart-Harris R. L. (2018). Serotonin, psychedelics and psychiatry. World psychiatry : official journal of the World Psychiatric Association (WPA), 17(3), 358–359.
  6. Vaughn, S. E., Strawn, J. R., Poweleit, E. A., Sarangdhar, M., & Ramsey, L. B. (2021). The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations. Journal of personalized medicine, 11(7), 615.
  7. Jenny, M., Schröcksnadel, S., Überall, F., & Fuchs, D. (2010). The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism. Pharmaceuticals (Basel, Switzerland), 3(8), 2647–2660.
  8. Lu, H. C., & Mackie, K. (2021). Review of the Endocannabinoid System. Biological psychiatry. Cognitive neuroscience and neuroimaging, 6(6), 607–615.
  9. Canal C. E. (2018). Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action. Handbook of experimental pharmacology, 252, 227–260.

Note: The content on this page is for informational purposes only and is not intended to be professional medical advice. Do not attempt to self-diagnose or prescribe treatment based on the information provided. Always consult a physician before making any decision on the treatment of a medical condition.

This article was published in March 2023 and most recently updated April 22, 2024.

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