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Serotonin Definition, Function & Effects of High/Low Levels

Written by Ana Aleksic, MSc (Pharmacy) | Reviewed by Biljana Novkovic, PhD | Last updated:
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Serotonin is both a hormone and neurotransmitter. It is essential for regulating mood, movement, sleep & much more. What else does it do, and what happens when it’s out of balance? Read on to find out more!

What is Serotonin?

Definition & Overview

Serotonin is an important signaling molecule throughout the brain and body. It is commonly known as the “happiness neurotransmitter” or the “happiness hormone” due to its prominent role in regulating mood.

Serotonin plays an important role in the brain, where its main job is to transmit messages between nerve cells. According to some scientific theories, serotonin is involved in all aspects of human behavior [1, 2].

However, brain serotonin makes up less than 2% of the total serotonin found in our bodies. Most serotonin (over 90%) is actually made, stored, and released by the gut. In addition, about 5-8% of serotonin is stored in platelets circulating in the blood [1, 3, 4].

As such, the roles of serotonin in the body are many and diverse. Research suggests that serotonin influences [4, 1, 3, 5, 2]:

  • Mood and emotions
  • Movement (motor function)
  • The sleep-wake cycle
  • Body temperature (thermogenesis)
  • Appetite
  • Bowel movements
  • Various gut functions
  • Blood clotting (platelet aggregation)
  • Constriction and relaxation of blood vessels (vasoconstriction and vasodilation)
  • Immune responses
  • Bone development
  • Heart function
  • Reproductive function & sexual behavior
  • Pain perception
Serotonin, the “happiness hormone,” is both a hormone and a neurotransmitter. It helps regulate many essential functions of the body, from mood and sleep to blood clotting and immune response.

What Does Serotonin Do?

Originally discovered in the 1940s, serotonin — also known as 5-hydroxytryptamine, or “5-HT” for short — is currently believed to play many pivotal roles in mood, behavior, gut, and overall optimal body function (homeostasis). So-called “imbalances” or other abnormalities in serotonin function have been linked with symptoms that may interfere with mental and physical health, and which can significantly impair quality of life [6, 7, 8].

According to some hypotheses and limited research, increasing serotonin levels may help with anxiety, depression, migraines, and constipation-predominant irritable bowel syndrome. However, more large-scale studies are needed [6, 7, 8].

Production and Removal

The majority of serotonin is made, stored, and released by cells in the gut lining (enterochromaffin cells). These cells make serotonin from the amino acid L-tryptophan, which is the main “building block”, or metabolic precursor of serotonin [9, 10].

Certain specific types of bacteria in the human digestive tract are believed to boost serotonin production in the gut. Gut flora actually balances tryptophan metabolism (via the kynurenine pathway), influencing the amount of L-tryptophan available for making serotonin. [11, 12].

However, serotonin produced by the gut cannot cross the blood-brain barrier. That is why brain cells must produce their own serotonin, either from L-tryptophan or 5-hydroxytryptophan (5-HTP), a byproduct of L-tryptophan [13, 14].

Conversely, excess serotonin and the brain and gut is “deactivated” by several different mechanisms. For example, proteins called serotonin transporters effectively “clean up” or “remove” (re-uptake) serotonin from neural synapses, and bring them back into neurons where it can be reused [15, 9].

Alternatively, serotonin that is released into the bloodstream either gets taken up (absorbed) by platelets, or is broken down (metabolized) in the liver and lungs by enzymes called monoamine oxidase (MAO-A), aldehyde, and alcohol dehydrogenase [3].

Serotonin is produced from tryptophan, both in the gut and the brain, where it performs different functions. Eventually, it is broken down by monoamine oxidase enzymes and other mechanisms. The relative balance between how quickly serotonin is produced and subsequently broken down is one of the main factors that determines how much available, “active” serotonin a person has.

Other Neurotransmitters

Monoamines

Serotonin is just one member of the “monoamine” family of neurotransmitters, which also includes other major neurotransmitters such as norepinephrine and dopamine. Researchers currently believe that all of these neurotransmitters work together to influence and regulate mood [16].

By extension, a person’s levels of each of these neurotransmitters may affect their mood. For example, a meta-analysis of data from more than 50 different studies reported that artificially depleting the levels of these neurotransmitters can cause “low mood” and other related symptoms (this is typically done by depleting the body of the metabolic precursors needed to make these neurotransmitters, such as tryptophan or tyrosine). However, these effects were only observed in individuals who had certain pre-existing risk factors — such a prior diagnosis of depression, or a family history of depression disorders — and are not necessarily seen in otherwise healthy people [16].

Imbalances in the levels or relative activity of serotonin, dopamine, and norepinephrine have also been proposed to play a role in other common psychiatric conditions, such as bipolar disorder [17].

However, some researchers have proposed that combined low levels of these three neurotransmitters — and not just low serotonin alone — may be important for understanding how these mood disorders originally develop and progress [17].

Hormones

In the pineal gland, serotonin is used to make melatonin, a hormone that synchronizes the body’s “biological clock” or circadian rhythm. When serotonin is low, that limits the amount of melatonin that can be made in the body, potentially interfering with the sleep-wake cycle [5].

Serotonin is one of the primary “monoamine” neurotransmitters, along with dopamine, norepinephrine, and others. These neurotransmitters (and the balance between them) are all believed to be essential for mental health and the sleep-wake cycle, among other important functions.

Associated Health Conditions & Disorders

Note that when we talk about serotonin-associated disorders, it’s important to realize that these disorders are not necessarily directly due to serotonin levels or production per se. Rather, they may instead stem from issues with serotonin reuptake, or the availability of certain serotonin receptors. There are over 15 different receptor types discovered to date, including the well-known 5-HT1A, 5-HT2A, and 5-HT2C [18, 19, 20].

Additionally, the majority of studies covered in this article deal with associations only, which means that a direct cause-and-effect relationship hasn’t yet been conclusively established.

For example, just because depression has been associated with low serotonin in certain brain areas doesn’t mean that depression is actually directly caused by low serotonin. Data are lacking to make such claims.

Also, even if a study did find that low brain serotonin contributes to depression, serotonin levels are highly unlikely to be the only causative factor. Complex disorders like depression always involve multiple possible factors — including brain chemistry, environment, health status, and genetics — which may vary from one person to another, and which may interact in highly complex ways to cause any particular effect on health or well-being.

With this in mind, limited studies have linked abnormal serotonin levels with [2, 4, 1, 21, 22]:

  • Various mental health conditions and psychiatric disorders, such as depression, anxiety, aggression, obsessive-compulsive disorder (OCD), substance abuse, and schizophrenia
  • Irritable bowel syndrome (IBS)
  • Heart disease
  • Osteoporosis

Additionally, scientists believe serotonin connects the gut microbiome with the brain – forming the so-called “gut-brain axis.” Decreased diversity and stability of beneficial gut bacteria has been linked with serotonin-related health issues — especially in the elderly [23, 24, 25].

Many different psychiatric disorders and other health conditions have been associated with abnormal serotonin levels. These include depression, anxiety, IBS, heart disease, and osteoporosis. However, “low” levels or other dysregulations of serotonin may not necessarily be their sole or direct cause, as many diverse factors can all interact together in complex ways to produce these conditions or symptoms.

When To “Increase” Serotonin Levels?

Like any bioactive substance in the body and brain, serotonin levels need to be carefully balanced in order to ensure optimal overall health.

However, this important fact sometimes gets lost in the way that many people discuss certain popular health topics, such as serotonin and dopamine levels. Unfortunately, it’s often possible to come away with the impression that having “more” of these is always “better” — which is definitely not the case!

For example, elevated levels of serotonin can cause serotonin syndrome — a serious medical condition that can be potentially fatal [26, 27, 28].

Additionally, increasing serotonin levels can sometimes worsen the symptoms of other pre-existing conditions (such as OCD) [29, 30, 31].

Therefore, it shouldn’t be assumed that increasing serotonin levels or activity is necessarily always a good thing. For this reason, it is crucially important to always talk to your doctor first before deciding to try any lifestyle changes or new supplements, as only a qualified medical professional can help you determine the most effective and safest course of treatment for you, based on your specific health needs and medical history.

Testing Serotonin

Serotonin that gets released into the blood gets rapidly broken down in the liver and lungs, to inactive metabolites (such as 5-HIAA) that are eventually excreted in urine [3].

This is why blood and urine typically contain trace amounts of serotonin. By extension, a person’s level of serotonin in these bodily fluids can sometimes be a useful diagnostic marker for serotonin-related abnormalities and health conditions. For example, larger quantities of serotonin in the blood/urine can be observed in people with serotonin-producing tumors (carcinoid tumors).

Nonetheless, there are a wide range of important limitations that reduce the reliability of urine tests when trying to “estimate” the actual levels of serotonin available in the brain. For example [32]:

  • Serotonin generally doesn’t cross the blood-brain barrier (BBB), meaning that the levels of serotonin in the blood don’t necessarily match up with the levels of active serotonin in the brain.
  • Even if serotonin did cross the BBB, it is released intermittently, and can be influenced by many different stimuli and other unpredictable factors. This means that a single measurement at a single point in time is not necessarily a reliable indicator of a person’s “normal” or “typical” levels of serotonin.
  • Furthermore, serotonin levels can vary quite a bit across different parts of the brain — so, once again, any single measurement might not necessarily say anything about how a specific part of the brain is using serotonin.
  • Finally, serotonin levels can vary for the same person from one day to another — so in reality, its levels would have to be tested multiple times on different days to get a reliable “snapshot” of a person’s overall levels of serotonin.

For these reasons, it is useful to remain skeptical about the use of urine serotonin levels to check for so-called “neurotransmitter imbalances.” While many companies that provide these tests state that the levels in urine directly and reliably correspond to brain neurotransmitter levels, research has repeatedly shown that this is not necessarily the case [32].

In addition, many of these companies have also been known to intentionally use extremely narrow reference ranges, without any scientific support whatsoever — often in order to sell supplements to their clients [33]!

By contrast, more reliable tests of serotonin levels include cerebrospinal fluid (CSF) tests, or measurements of serotonin in blood platelets. This is because these measurements are either more “direct” measurements of serotonin in brain and nervous system (such as for CSF tests), or are based on measurements that are more “stable,” and have less sudden fluctuations over time (such as for platelet tests) [34, 35].

Ultimately, however, getting a PET scan is really the only “direct” way to accurately and reliably detect changes of serotonin production in specific areas of the brain [35].

Brain serotonin is challenging to measure. Serotonin does not cross the blood-brain barrier, which means that urine and blood tests are often not helpful or reliable. Currently, the only way to measure brain serotonin directly is by getting a PET scan.

Risks and Safety

Like any bioactive compound, serotonin (and the substances that potentially influence it) have the possibility of causing adverse side-effects and other potential risks and dangers.

Additionally, any substance or other factor that can influence serotonin levels also has the potential to have unpredictable and negative interaction with other dietary factors, supplements and medications, pre-existing health conditions, and other important health-related factors.

Therefore, always make sure to discuss any new supplements or lifestyle changes with your doctor first. Also make sure that he- or she is fully aware of any other relevant factors (such as special diets, current medications, or supplements) that may impact your health. The information in this post should never be used to replace conventional treatment.

Serotonin Syndrome

Excess serotonin may result in serotonin syndrome, which often results from adverse drug interactions, and which can be fatal [36].

MDMA, LSD, and other synthetic drugs may cause serotonin syndrome, and should not be taken without medical supervision or outside a psychotherapeutic environment [37].

>>> To learn more about serotonin syndrome, you can check out our detailed and comprehensive post on it here.

Drug Interactions

The use of St. John’s Wort, SAM-e, or lithium simultaneously with serotonergic drugs such as selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), or triptans can greatly increase the risk of serotonin syndrome, a life-threatening and potentially fatal condition [26, 27, 28].

Other Potential Risks

Abnormally heightened blood levels of serotonin (hyperserotonemia) is a consistent finding in individuals with autism. Relatedly, pregnant women with hyperserotonemia have been reported to be more likely to give birth to children with autism [38, 39].

When it comes to serotonin, “more” does not always equal “better”! There are some potential risks associated with elevated serotonin that it is important to be aware of. For example, excess serotonin can cause serotonin syndrome, a potentially life-threatening condition.

Further Reading

Takeaway

Serotonin is an important signaling molecule throughout the brain and body. It is commonly known as the “happiness neurotransmitter” or the “happiness hormone” due to its prominent role in regulating mood.

The majority of the serotonin in the human body is made and metabolized entirely in the gut. The brain must produce its own serotonin, as this hormone cannot cross the blood-brain barrier.

Serotonin has a vast array of known and suspected functions, including in regulating mood (a task it appears to share with other neurotransmitters like dopamine), movement, sleep, body temperature, appetite, gut function, blood clotting, immune response, and much more.

Imbalances in the serotonin system have been associated with such diverse conditions as migraines, mental illness (chiefly, depression), irritable bowel syndrome (IBS), heart disease, and osteoporosis.

Too much serotonin in the body can result in serotonin syndrome, a potentially life-threatening condition. Combining any drugs or supplements that can increase serotonin may increase a person’s risk of serotonin syndrome. Talk to your doctor before using any such substances.

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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