What Does Serotonin Do?

Serotonin is a neurotransmitter that regulates mood, sleep, appetite, and cognitive functions. Though primarily found in the intestines, its presence in the brain affects emotional well-being and mental health. Abnormal serotonin levels are linked to depression and anxiety.

Serotonin’s Role in the Brain

Serotonin and Behavior

Serotonin is projected from the brain stem and reaches most regions of the brain, giving it a wide array of effects on many aspects of behavior:

• Controls attention, perception, and memory
• Regulates anger and aggression
• Influences reward processing and motivation
• Affects motor skills and coordination
• Manages appetite and eating behaviors
• Modulates impulsivity and decision-making

Did you know? It is difficult to identify a human behavior that is not regulated by serotonin in some way.

Serotonin and Mood

Serotonin is one of the key neurotransmitters involved in modulating mood, since it:

• Acts as a natural mood stabilizer
• Promotes feelings of happiness and emotional stability
• Helps regulate anxiety levels
• Works with other neurotransmitters (like dopamine) to balance emotions
• Contributes to self-esteem and emotional well-being
• Influences frustration tolerance and irritability levels

Serotonin and Sleep

Serotonin helps regulate sleep by stimulating parts of the brain that control sleep and wakefulness:

• Controls when we fall asleep and wake up
• Regulates sleep patterns through specific brain receptors
• Serves as a precursor to melatonin production
• Different serotonin receptors determine sleep vs. wakefulness states
• Influences sleep quality and duration

Serotonin’s Role in the Body

Outside of brain functions, serotonin also plays a big role in physical health:

• Maintains digestive function
• Promotes healthy bone density
• Assists in blood clotting and wound healing
• Controls cardiovascular function
• Regulates bladder control and bowel movements
• Influences sexual function
• Helps maintain body temperature
• Affects muscle contraction and relaxation

Did you know: Most of the body's serotonin is found in the gastrointestinal tract rather than the brain.

How Does Serotonin Work?

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter made from the essential amino acid tryptophan.

Where Serotonin Is Made

Most of the body’s serotonin (around 90%) is produced in the gastrointestinal (GI) tract, particularly by enterochromaffin cells in the gut lining.

The remaining 10% is synthesized in the brain, specifically in a group of neurons located in the Raphe nuclei, which are clustered in the brainstem.

Serotonin is made from tryptophan in two steps. An enzyme called tryptophan hydroxylase converts tryptophan into 5-HTP, the slowest and rate-limiting step, before a second enzyme converts 5-HTP into serotonin itself.

Because this enzyme isn’t saturated, how much tryptophan reaches the brain controls how much serotonin gets made. A very low-tryptophan diet can lower brain serotonin within hours.

From the Raphe nuclei, serotonergic neurons project throughout the brain. They reach the limbic system, prefrontal cortex, hippocampus, and basal ganglia, allowing serotonin to influence mood, memory, learning, and movement.

How Serotonin Communicates

Serotonin is released from the presynaptic neuron into a tiny gap called the synaptic cleft. From there, it can do one of several things:

• Bind to serotonin receptors on the postsynaptic neuron, such as 5-HT1A, 5-HT2A, and 5-HT3, each producing different effects depending on where they sit.
• Be taken back up by the presynaptic cell using a protein called the serotonin transporter (SERT). This process is called reuptake.
• Be broken down by an enzyme called monoamine oxidase (MAO) if not reabsorbed.

Depending on the receptor type and brain region, serotonin can be excitatory (stimulating neurons) or inhibitory (calming activity).

This is why it has such a wide range of effects, from stabilizing mood to helping regulate sleep, digestion, and blood clotting.

What Happens When Serotonin Is Low?

Low serotonin levels in the brain can affect both mental health and bodily functions, contributing to a wide range of symptoms.

This imbalance is often linked to conditions like depression, anxiety disorders, insomnia, and even irritable bowel syndrome (IBS).

Common Symptoms of Low Serotonin

When serotonin levels are low, people may experience:

• Persistent low mood or sadness
• Increased anxiety, irritability, or aggression
• Low self-esteem or negative self-perception
• Sleep problems, including insomnia or disturbed sleep
• Changes in appetite, often reduced hunger
• Poor memory or concentration
• Difficulty controlling impulses or making decisions

In more severe cases, low serotonin may also play a role in obsessive-compulsive behaviors, chronic pain, and fatigue.

Low serotonin is also associated with mood disorders such as major depressive disorder (MDD) and generalized anxiety disorder (GAD).

It may also contribute to schizophrenia, post-traumatic stress disorder (PTSD), and eating disorders.

Increasing Serotonin Levels

Increasing serotonin levels can enhance mood, alleviate depression, and regulate sleep and appetite. Proper serotonin balance is essential for emotional and mental well-being.

While medications are often prescribed to treat symptoms associated with low serotonin, there are also natural ways to boost serotonin levels:

• Exercise: Regular physical activity can increase serotonin production and release. Aerobic exercise, such as running, cycling, or swimming, has been shown to have mood-boosting effects.
• Sunlight exposure: Vitamin D, which is produced when the skin is exposed to sunlight, is important for serotonin synthesis. Spending time outdoors or using light therapy can help boost serotonin levels.
• Stress reduction: Chronic stress can deplete serotonin levels. Engaging in stress-reducing activities like meditation, yoga, or deep breathing exercises can help maintain healthy serotonin levels.
• Sleep: Adequate, quality sleep is crucial for serotonin regulation. Aim for 7-9 hours of sleep per night and maintain a consistent sleep schedule.

Medications That Affect Serotonin

Selective Serotonin Re-uptake Inhibitors (SSRIs): The most prescribed antidepressants, SSRIs work by blocking the re-uptake of serotonin, making more available in the brain. Examples include Citalopram (Celexa), Fluoxetine (Prozac), and Sertraline (Zoloft).

SSRIs block reuptake within hours, yet most people feel no mood benefit for two to several weeks. One explanation points to the brain’s own feedback receptors.

The initial rise in serotonin first quiets serotonin-producing neurons through these receptors. That feedback fades over weeks. Serotonin transmission then actually increases (Harmer et al., 2017).

Tricyclic antidepressants (TCAs) and Monoamine oxidase inhibitors (MAOIs): Older classes of antidepressants that also increase serotonin levels, but with more side effects compared to SSRIs.

While medications can be effective for treating serotonin imbalances, it’s important to work with a healthcare provider to find the right treatment plan.

Incorporating natural methods to boost serotonin, alongside medical treatment when necessary, can help promote overall emotional well-being.

What Happens When There’s Too Much Serotonin?

Serotonin supports a good mood. Too much of it, however, can be harmful.

A surplus can come from the very medications used to treat low serotonin, or from combining more than one serotonergic drug at once. This overload can trigger serotonin syndrome, a potentially dangerous reaction (Boyer & Shannon, 2005).

This syndrome can arise after starting a new medication or raising an existing dose.

Milder symptoms include:

• Confusion
• Dilated pupils
• Restlessness
• Rapid heart rate
• High blood pressure
• Headaches
• Shivering and goose bumps

Mild cases often clear up within a day of stopping the drug involved. Untreated cases can worsen into seizures, an irregular heartbeat, unconsciousness, or death.

Anyone starting medication for low serotonin should begin with a low dose and increase it only under medical guidance.

Critical Evaluation

Serotonin clearly shapes mood, sleep, and behavior. Yet its most famous clinical claim, that low serotonin causes depression, has not survived close scientific scrutiny.

Is Depression Really Caused by Low Serotonin?

Aim: Moncrieff and colleagues (2022) set out to test a specific, influential claim. Does depression really come from low serotonin?

Method: Their systematic umbrella review pooled dozens of studies across five research areas: serotonin and its metabolites in body fluids, receptor and transporter imaging, tryptophan-depletion experiments, and gene-by-stress studies.

Results: The largest, highest-quality studies showed no consistent evidence linking depression to lowered serotonin. Two genetic studies covering over 150,000 people combined, among the largest ever conducted, found no link at all. Imaging and metabolite studies gave only weak, inconsistent evidence.

Evaluation: Not everyone agrees this settles the debate.

Conclusion: The review found no support for the low-serotonin theory of depression. It challenges the popular chemical-imbalance explanation directly, though it does not prove serotonin plays no role in mood at all.

Counter-Arguments and the Downstream View

Not every researcher accepts Moncrieff’s conclusion as the final word.

Cowen and Browning (2015) point out that tryptophan depletion still worsens mood in vulnerable people, so serotonin clearly plays some part even without a simple deficit.

The efficacy of SSRIs never actually depended on the chemical-imbalance theory being true. A drug can still help without the disorder being a deficiency of its target, just as aspirin easing a headache does not make headaches an aspirin deficiency.

Contemporary accounts locate the real action further downstream.

Harmer and colleagues (2017) argue SSRIs may work through neuroplasticity, brain changes that build new connections. An early shift in how the brain processes emotional information may come first, with felt mood improvement only following later.

Beyond the serotonin-depression debate, psychologists raise several broader criticisms of reducing behavior to one chemical:

• Reductionism: Explaining a complex, socially embedded experience like depression through one molecule oversimplifies a system that also involves other transmitters, hormones, and life experience.
• Correlation, Not Causation: Most human evidence is correlational, so it cannot show that a serotonin change caused a disorder rather than resulting from it.
• Oversimplified Marketing: The “chemical imbalance” idea was always a simplification rather than an established finding, and its collapse risks discouraging people from effective treatment.
• One Transmitter, Many Effects: Serotonin acts on at least fourteen different receptors with both excitatory and inhibitory effects, so no single behavior can be “the serotonin behavior.”

Contemporary Research

Two lines of newer evidence are reshaping how psychologists think about serotonin. The first concerns psychedelic drugs.

Carhart-Harris and colleagues (2016) gave psilocybin, the active compound in “magic mushrooms,” alongside psychological support to patients with treatment-resistant depression in an open-label feasibility study. Mood improved rapidly, and the effect lasted for some patients at three-month follow-up.

The second concerns the gut. Because most of the body’s serotonin is made there, researchers now study how the gut microbiome and enteric serotonin communicate with the brain. This gut-brain axis reframes serotonin as a whole-body signal rather than a purely mental one (Banskota et al., 2019).

References

Banskota, S., Ghia, J. E., & Khan, W. I. (2019). Serotonin in the gut: Blessing or a curse. Biochimie, 161, 56-64. https://doi.org/10.1016/j.biochi.2018.06.008

Berger, M., Gray, J. A., & Roth, B. L. (2009). The expanded biology of serotonin. Annual Review of Medicine, 60, 355-366. https://doi.org/10.1146/annurev.med.60.042307.110802

Boyer, E. W., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352(11), 1112-1120. https://doi.org/10.1056/NEJMra041867

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H., & Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. The Lancet Psychiatry, 3(7), 619-627. https://doi.org/10.1016/S2215-0366(16)30065-7

Cowen, P. J., & Browning, M. (2015). What has serotonin to do with depression? World Psychiatry, 14(2), 158-160. https://doi.org/10.1002/wps.20229

Harmer, C. J., Duman, R. S., & Cowen, P. J. (2017). How do antidepressants work? New perspectives for refining future treatment approaches. The Lancet Psychiatry, 4(5), 409-418. https://doi.org/10.1016/S2215-0366(17)30015-9

Lane, R., Baldwin, D., & Preskorn, S. (1995). The SSRIs: Advantages, disadvantages and differences. Journal of Psychopharmacology, 9(2 Suppl.), 163-178. https://doi.org/10.1177/0269881195009002011

Mayo Clinic. (2019, October 8). Tricyclic antidepressants and tetracyclic antidepressants. https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046983

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28, 3243-3256. https://doi.org/10.1038/s41380-022-01661-0

Further Reading

Olivier, B. (2015). Serotonin: A never-ending story. European Journal of Pharmacology, 753, 2-18.

Lin, S. H., Lee, L. T., & Yang, Y. K. (2014). Serotonin and mental disorders: A concise review on molecular neuroimaging evidence. Clinical Psychopharmacology and Neuroscience, 12(3), 196-202.