Can You Get Serotonin Syndrome From Cannabis?

May 31, 2023
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Can you get serotonin syndrome from smoking weed? 

Is there a link between cannabis and serotonin toxicity? In short, the chances of experiencing serotonin syndrome — a condition caused by dysregulation of the neurotransmitter serotonin — is unlikely to occur from cannabis consumption alone.

In fact, you’re more likely to experience serotonin syndrome after consuming one or more of a variety of pharmaceutical medications that influence how your body makes and utilizes serotonin.

Readers who take antidepressant medications may experience some side effects such as headaches or nausea, especially when adjusting dosage or medication type. However, these symptoms are typically related to the body adapting to the new medication, rather than an indication of serotonin syndrome, which is a specific and potentially severe condition.

Still, researchers have raised some concerns regarding interactions between cannabis, the body’s endocannabinoid system, and the internal systems that regulate serotonin.

Read on to learn more about serotonin syndrome and what the current literature reveals about the risk cannabis consumption could present.

What is serotonin syndrome?

To understand whether there is a connection between serotonin syndrome risk and marijuana, we’ll first need to understand what serotonin is and what it does.

Serotonin, or 5-Hydroxytryptamine (5-HT), is a neurotransmitter with a “wide range of functions in the central nervous system (CNS), including modulation of attention, cognition, behaviour, memory, and thermoregulation.”

Serotonin also has several functions “in the peripheral nervous system (PNS), where it regulates, for example, gastrointestinal (GI) motility, uterine contraction, vasoconstriction, and bronchoconstriction.”

Serotonin syndrome occurs when there is an excess of serotonin-related activity in the CNS. This is most frequently seen in cases where multiple compounds impacting serotonin are acting upon the body.

The condition has been observed “across the full range of age groups,” an overview published in 2019 reports, adding that serotonin syndrome might appear in emergency rooms with greater frequency as more and more individuals are prescribed antidepressant medications.

The symptoms for serotonin syndrome vary depending on the intensity of the patient’s condition and tend to present both physically and in the patient’s mental state. For mild cases, symptoms might include gastrointestinal distress in the form of diarrhea or nausea, as well increased blood pressure, increased heart rate, inducible clonus (a type of reactive muscle reflex), and feelings of anxiety.

For moderate cases, symptoms will likely be similar to mild cases but will present with greater intensity. Patients might experience muscle tremors, hyperthermia, and flushed skin. They might also feel agitated to a degree beyond baseline anxiety and display abnormal eye movement.

For the most severe cases, patients might experience “hyperactive bowel sounds, delirium, and muscle rigidity” in addition to the symptoms that appear in moderate cases. Severe cases can be further complicated by seizures and acute respiratory distress syndrome, among other symptoms, and can even result in death.

Marijuana and serotonin syndrome

There is little clear evidence regarding the impact of cannabis consumption on how your body creates and uses serotonin. While it has been established that the endocannabinoid system and the serotonergic system (which regulates serotonin) have overlapping interactions and functions, the specifics of what results from that overlap remain undetermined.

For example, one 2021 review examining the impact of cannabis on the sleep cycle in relation to serotonin (which plays a role in regulating the sleep-wake cycle, though experts disagree on its exact role) states that “cannabinoids and the endocannabinoid system modulate serotonergic signaling in the CNS,” adding that there is “a high level of functional overlap between [the] serotonergic and endocannabinoid systems.”

The actual interactions of these two systems, however, remains unclear, the authors report.

Another study, published in 2020, found that long-term exposure of rodents to low levels of THC “increased anhedonia and anxiety-related behavior paralleled by a decrease in serotonin activity, which is the main neurotransmitter implicated in depression.”

“Similarly, adults exposed to THC presented decreased serotonin activity, suggesting that THC may induce vulnerability in the monoaminergic system, even if the behavioral effects are more pronounced in adolescents,” the authors add.

“Importantly, these depressive phenotypes were not observed in adult exposure, suggesting that the emotional liabilities during adolescence were linked to an age-dependent vulnerability of the developing serotonergic system.”

The results of this second study suggest that, if cannabis consumption is likely to have an impact on serotonin in humans, that impact is most likely to occur among young consumers with underdeveloped serotonergic systems. 

A much earlier study, published in 2005, suggests that chronic cannabinoid consumption might impact 5-HT2a and 5-HT1a receptors in rodents (both of which are serotonin receptors) in a manner that causes the receptors to behave similarly to how they sometimes do in individuals diagnosed with depression.

According to the study’s authors, their data is the first to “demonstrate that chronic cannabinoid treatment can modify the 5-HT system.”

Interestingly, one study published in 2018 that focused on the impact of CBD on brain serotonin levels found that “the antidepressant-like effect induced by CBD in the [forced swim test] is dependent on serotonin levels in the CNS.”

The antidepressant properties of CBD in lab settings are well established, but this study further advances our understanding of the interaction between the serotonergic system and an increasingly popular, non-intoxicating cannabinoid by showing an interaction between weed and serotonin levels.

Diagnostic difficulties: cannabis toxicity vs. serotonin syndrome

Cannabis toxicity, a term used to describe the overconsumption of cannabis or cannabinoids, is sometimes mis-diagnosed by clinicians as serotonin syndrome, according to a 2020 journal article that examined two such cases.

“Although the cases did not show all of the hallmarks of a true serotonin syndrome, some overlap existed in physical exam findings,” the authors state.

“Our cases reflect that adolescents who abuse THC by heating and then inhaling the concentrated vapor, can present with signs and symptoms that mimic serotonin syndrome. For that reason, high-potency marijuana abuse should be considered when encountering young adults in the [emergency department] with these exam findings.”

Another case study, published two years later, tells a similar story about a patient who had an adverse response after overconsuming high-potency dabs via a vape pen.

“Since dab overuse and serotonin syndrome may present with similar clinical findings, one should have a high level of suspicion when treating patients with history of substance use and those taking medications that can increase serotonin levels,” the authors write. 

“Thus, both serotonin syndrome and cannabis intoxication should be considered in the differential diagnosis of a patient with these similar clinical features.”

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