Does Marijuana Affect Serotonin?

May 17, 2023
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Dr. David Pompei, PharmD, MS

Does marijuana affect serotonin?

Did you know that cannabis affects serotonin levels? New research suggests that marijuana use may cause some changes in serotonin functioning. Read on to learn more about the link between marijuana and serotonin, and how this relationship could impact your mood.

What is serotonin?

Serotonin, or 5-Hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a complex and multi-faceted function. Serotonin is involved in mood, learning, memory, as well as physiological processes like vasoconstriction or vomiting.  

Over 90% of all serotonin in the body is located within the gastrointestinal tract, where it is used to regulate intestinal movements. 

However, serotonin is much more well-known for its role in the brain. Serotonin is often called the "happiness hormone" due to its role in modulating impact mood, appetite, and sleep. Several classes of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) target the serotonergic system.

Serotonin levels usually are low in people who suffer from depression. Several supporting studies have been published, most notably a 2015 study by Philip J. Cowen and Michael Browning published in the Journal of World Psychiatry, which associated serotonin with depression. Recent research indicates that other factors may be involved in depression, such as brain-derived neurotrophic factor (BDNF). 

Does cannabis increase serotonin?

Does cannabis increase serotonin? There isn’t a simple answer to this question. The endocannabinoid system and the serotonin system have a complex relationship. For example, both systems are involved in appetite, sleep, and emotional processes. Additionally, cannabis contains many different chemicals including cannabinoids, terpenes, and flavonoids—many of which may exert biological effects. 

However, animal studies indicate that a low dose of a CB1 receptor agonists like THC acutely increases serotonin, but a high dose produces the opposite effect: decreasing serotonin neurotransmission.

Many people want to know, “does THC release serotonin?” 

Does THC release serotonin? 

THC has been shown to inhibit serotonin re-uptake—which is how SSRIs work. In short, THC doesn’t “release serotonin,” but low dose THC may increase the level of serotonin neurotransmission. However, long-term (chronic) cannabis use produces a different effect on the serotonin system.

For example, long-term cannabinoid administration alters 5-HT receptor signaling by upregulating 5-HT2A gene activity and downregulating 5-HT1A gene activity. These results are noteworthy, as a similar finding has been observed in depression. These two receptors appear to “elicit opposing behavior” with 5-HT1A activation inducing anxiolysis (decreased anxiety) and 5-HT2A activation inducing anxiety. 

Because cannabis does affect serotonin, cannabis overdoses can mimic the symptoms of serotonin syndrome. 

Serotonin syndrome symptoms: what are they?

Serotonin syndrome is a potentially fatal adverse drug reaction caused by excessive serotonergic activity in the central nervous system and periphery.  

This condition usually occurs when you star taking a new drug or increase your dose of antidepressants. Symptoms can include:

●      High blood pressure

●      Agitation

●      Accelerated heartbeat

●      Abnormally dry mouth

●      Confusion

●      Extreme aggressiveness

●      Jerky movement of the eyes

●      Dilated pupils

●      Restlessness, characterized by a sense that one needs to be constantly moving

●      Extremely sensitive reflexes

●      Muscle spasms

●      Uncontrollable twitches

●      Tremors

●      Full-body seizures

●      Sweating

●      Shivering

●      High fever – over 104°

●      Increased bowel sounds

●      Diarrhea

●      Death

Can marijuana cause serotonin syndrome?

Does marijuana increase serotonin? At low doses, marijuana increases serotonin levels, leading to feelings of pleasure and well-being. On the other hand, higher doses of THC have the opposite effect. But if cannabis can increase serotonin, can you get serotonin syndrome from weed? 

While there are anecdotal reports of cannabis-induced serotonin syndrome, there are no peer-reviewed case studies linking serotonin syndrome to cannabis. 

However, acute cannabis toxicity (a weed overdose) can resemble serotonin syndrome. A

So just how does weed deplete serotonin? When marijuana intake is high, THC inhibits serotonin reuptake, which may lead to depression as potent cannabinoid receptor agonists activate the brain's serotonin receptors. 

As more states legalize marijuana, the potential for high-potency marijuana abuse could lead to an increase in the number of emergency department (ED) visits. For example, a 2020 case study describes a pair of teenage patients who presented to the emergency department with dilated pupils, stiffness in both legs, and convulsions in both feet following inhalation of a cannabis concentrate. 

Serotonin syndrome was initially considered, but the patients were both eventually diagnosed with cannabis toxicity. For that reason, it's helpful to remember that both serotonin syndrome and cannabis toxicity should be considered in cases where serotonin syndrome is suspected. 

Can CBD cause serotonin syndrome?

In 2014, an animal study showed that CBD interacts with serotonin and may have mild antidepressant and sedative properties. If you are only taking CBD, CBD can’t cause serotonin syndrome. 

However, CBD interacts with drug-metabolizing enzymes and has been shown to interact with various antidepressants. CBD combined with antidepressants could potentially cause serotonin syndrome. If you are taking an SSRI, talk to your doctor before adding cannabis or CBD into your routine.

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