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Major Depression Serotonin Precursors: 5-HTP

5-hydorxytryptophan (5-HTP) is a compound made from the amino acid (protein) tryptophan and is primarily found in the brain. 5-HTP is one of the basic building blocks for serotonin. Serotonin itself can be manufactured in the laboratory, but when taken as a supplement, it cannot reach the brain (it does not have the ability to cross from general blood circulation into brain circulation, because of the blood-brain barrier; a selective membrane that only allows certain chemicals into the brain). Multiple research studies support the use of 5-HTP as a natural way to increase brain serotonin levels. Some research has also supported the use of 5-HTP for treating depression, but the studies are based on small groups of people, limiting the conclusions that can be drawn about the potential benefits of 5-HTP as a generalized depression treatment.

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Key takeaways

  • 5-HTP is a serotonin precursor that has been investigated as a treatment for depression.
  • Small study samples limit confidence in its effectiveness as a general depression treatment.
  • Interactions with antidepressants and other safety concerns make professional guidance important before use.

Safety and Dosing

A typical dose of 5-HTP is between 150-300 mg a day. 5-HTP must not be used with any other antidepressant medication because of the risk of serotonin syndrome (or serotonin toxicity) that produces mental confusion, agitation, headache, shivering, sweating, hypertension (high blood pressure), tachycardia (fast heart rate), and other symptoms. 5-HTP also may interfere with lithium (a medication typically used for bipolar disorder).

The side effects of 5-HTP include: agitation, drowsiness, flushing, headache, mild stomach upset, and tachycardia (fast heart rate). There is a small risk of developing liver toxicity when using 5-HTP. L-tryptophan, a closely related chemical, was pulled from shelves in 1989 when it was associated with liver failure in a few people taking the supplement. While it appears that 5-HTP does not cause this problem, it is best to check with your health practitioner before starting any new medication, especially if you currently have (or have a history of) liver problems.

WARNING: Any substance that increases serotonin carries with it the risk of causing a manic episode in people with Bipolar Disorder (manic depression). While the use of 5-HTP hasn't been linked to manic episodes, caution is still warranted. Consult your health care provider before taking 5-HTP if you suspect you might have bipolar disorder.

Subject matter expert

Simone Hoermann Ph.D.

Personality disorders, anxiety, and depression

View experience

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