Serotonin advice

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract.

Serotonin was first recognized as a powerful vasoconstrictor in blood serum. It was isolated in 1948 by Page and was later found to be associated with the central nervous system.

The chemical name for serotonin is 5-hydoxytryptamine which is often abbreviated to 5-HT.

Serotonin is naturally produced in the pineal gland which lies at the center of the brain. The average adult human has 5 to 10 mg of serotonin in the body, 90 % of which is in the intestine and the rest in blood platelets and the brain.

Serotonin is a neurotransmitter, allowing numerous functions including the control of appetite, sleep, memory and learning, temperature regulation, mood, behaviour, cardiovascular function, muscle contraction, endocrine regulation and depression.

Serotonin is believed to play an important part of the biochemistry of depression, migraine, bipolar disorder and anxiety. It is also believed to influen sexuality and appetite.

Serotonin is found extensively in the human gastrointestinal tract, or gut, as well as in the blood stream.

Serotonin is synthesized in the body from the amino acid tryptophan by various enzymes.

Serotonin taken orally does not pass into the central nervous system (CNS). This is due to the blood-brain barrier preventing serotonin in the blood stream from affecting serotonin levels in the brain. However, the amino acid tryptophan and its metabolite 5-hydroxytryptophan, from which serotonin is synthesized, are capable of crossing the blood-brain barrier. These agents are available as dietary supplements and may be effective serotonergic agents.

Turkey is high in tryptophan and that is one reason for the sleepiness that follows a big Thanksgiving meal.

Serotonergic action is terminated primarily via uptake of 5-HT from nerve synapses.

Some drugs inhibit this re-uptake of serotonin, again making it stay in the synapse longer. The tricyclic antidepressants inhibit the re-uptake of both serotonin and norepinephrine. The newer selective serotonin re-uptake inhibitors (SSRIs) and selective serotonin and nor-epinephrine reuptake inhibitors (SNRIs)have fewer side effects and fewer interactions with other drugs.

5-HT3 antagonists such as ondansetron, granisetron and tropisetron are important antiemetic agents. They are particularly important in treating the nausea and vomiting which occur during anticancer chemotherapy using cytotoxic drugs.

Low serotonin levels are believed to be the cause of many cases of mild to severe depression.

If depression arises as a result of a serotonin deficiency then pharmaceutical agents that increase the amount of serotonin in the brain should be helpful in treating depressed patients. Anti-depressant medications increase serotonin levels at the synapse by blocking the reuptake of serotonin into the presynaptic cell. Anti-depressants are one of the most highly prescribed medications.

If depression is mild enough it can sometimes be managed without prescribed medications. The most effective way of raising serotonin levels is with vigorous exercise. Studies have shown that serotonin levels are increased with increased activity and the production of serotonin is increased for some days after the activity.

Serotonin levels can also be controlled through the diet. A diet deficient in omega-3 fatty acids may lower brain levels of serotonin and cause depression. Complex carbohydrates raise the level of tryptophan in the brain resulting in a calming effect. Vitamin C is also required for the conversion of tryptophan into serotonin.

Care must be taken in any attempt to increase serotonin levels, as a dangerous condition known as serotonin syndrome may result. This is especially a concern if multiple serotonergic agents interact to increase 5-HT levels - such as can happen when St Johns Wort is taken in combination with an SSRI.


Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5 ed). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4

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