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Tryptophan, an amino acid, is a precursor of serotonin and has been used since the 1970s to increase brain levels of serotonin.

5-HTP (5-hydroxy-L-tryptophan) is a modern variant, now extensively marketed in the United States. Before it was temporarily banned by the FDA (from 1989-2002), tryptophan was successfully used to supplement standard tricyclic antidepressants. It has been used successfully with MAOIs. Two meta-analyses, in 2004 and 2006, showed modest support for the use of 5-HTP as an adjunctive treatment for depression. Earlier studies had shown modest effectiveness for anxiety. As with tryptophan, the clinical activity of 5-HTP is believed to result primarily from its ability to act as a precursor of serotonin synthesis and increase central nervous system levels of serotonin.

Mental Health Implications

Depression and Anxiety

There are insufficient data to recommend use of tryptophan or 5-HTP, but there is enough promise to merit further research and cautious experimentation if standard treatments for depression or anxiety are ineffective or poorly tolerated. Mischoulon concludes that it is one of the safer of the natural products available for mood disorders, and previous evidence is supportive of its use for depression and anxiety. Mischoulon says that though it appears to act like an SSRI, he still would like to see a new wave of more rigorous research with current preparations before he proceeds to recommend it on the same platform with the better-tested SSRIs. Despite these evidentiary concerns, 5-HTP has been used clinically for over 30 years for the treatment of a wide variety of conditions, including:

  • fibromyalgia,
  • insomnia,
  • binge eating associated with obesity,
  • cerebellar ataxia, and
  • chronic headaches.
  • There is some risk, but it appears to be manageable.

Drug Interactions

Interaction with psychotropic drugs has been tested and appears generally safe, but no reported studies have been conducted with SSRIs. Thus, consumers should consult with the prescribing physician before using 5-HTP if they are currently being treated with a psychotropic drug, especially an SSRI.

Side Effects

The most common reported adverse effects are gastrointestinal, including nausea, vomiting, and diarrhea. Sedation is also a concern. These side effects are usually moderate and often abate or disappear once a steady dosage is achieved. Less common side effects may include headache, insomnia, and palpitations. Studies have shown no sign of toxicity. Generally, oral 5-HTP has been well tolerated. 5-HTP has not been studied in children or in pregnant or breast-feeding women. Accordingly, although there are no contraindications, it cannot be recommended.


Contaminated tryptophan caused an epidemic of eosinophilia-myalgia syndrome (EMS) that peaked in 1989. One researcher cautions that absent testing, tryptophan cannot be presumed to be safe, but others advise that while prescription tryptophan is now safe, consumers should be careful about purchasing non-prescription tryptophan. Thus, there is some risk of contamination with both tryptophan and 5-HTP, and consumers should buy these supplements only from reputable sources.


Promising, but not yet proven. With the exception of adjunctive use, which needs to be under physician supervision, 5-HTP is a reasonable choice if other treatments prove ineffective or are poorly tolerated.

For detailed information on SAM-e and other treatments, download the full review.

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