What is it?


5-Hydroxytryptophan (5-HTP) is used as an amino acid precursor to boost serotonin (scientifically known as 5-hydroxytryptamine or 5-HT) levels. (18) Serotonin is a neurotransmitter most commonly associated with the regulation of psychiatric and neurological activity, though it is also hormonally involved in most physiological processes in the body. (5) Until 1995, 5-HTP was previously only available via prescription in the United States, however, it is now regulated as a dietary supplement and available over-the-counter. It is most often sourced from the seeds of the African botanical Griffonia simplicifolia, which are composed of up to 20% 5-HTP, but it can also be synthesized from the amino acid L-tryptophan. (18)(19)(26)

Most trials on the primary use of 5-HTP in depression were conducted during the 1970s with very few being published thereafter. The low rates of new research on 5-HTP may have been linked to an initial association between tryptophan and the fatal eosinophilia-myalgia syndrome in 1989. However, it was later discovered that the cause of the syndrome was actually induced by product defects rather than the physiological response to tryptophan or 5-HTP itself. (21) Regardless, clinical evidence supporting the use of 5-HTP continues to be quite dated. Most work was conducted in the late 1900s and early 2000s with little research published within the last 10 years. This highlights the need for more up to date research, particularly considering 5-HTP’s potential applications in psychiatric and mental health.

Not be confused with: 5-HT (serotonin)


Main uses

Depression, anxiety, and behavioral disorders
Neurodevelopmental disorders
Neurological degeneration
Withdrawal symptoms


May lead to adverse effects (e.g., gastrointestinal distress, depressive moods, headaches, dizziness, or heart palpitations) related to rapid serotonin spikes and troughs due to quick absorption and elimination, respectively
Lower half-life with faster fluctuation in plasma levels may require more frequent administration, possibly leading to reduced relative compliance (19)
May possess fewer adverse events related to serotonin spikes and troughs due to slower absorption
May allow for higher dosing/efficacy and better compliance due to fewer required daily doses (19)

Dosing & administration

Adverse effects

Overall, 5-HTP monotherapy has a good safety profile and low likelihood to cause severe side effects. However, gastrointestinal distress or other mild events such as depressive moods, headaches, dizziness, or heart palpitations may occur. This may be attributed to the intolerance to rapid rises in serotonin levels, particularly if being used as an adjunct to other therapies such as selective serotonin reuptake inhibitors (SSRI). (19)

Long-term or high doses of 5-HTP may also deplete catecholamines, including dopamine, epinephrine, and norepinephrine. Some research suggests that long-term administration of 5-HTP should involve concomitant use of other serotonin or dopamine amino acid-precursors, such as L-tyrosine or L-dopa, to prevent amino acid or neurotransmitter depletion via competing for rate-limiting enzymes that produce catecholamines. (18)(21)

Practitioners should be aware that preclinical studies using extreme doses in combination with SSRIs have induced serotonin syndrome in rats, however, this has yet to be substantiated in humans. (19) 5-HTP may also induce anorexic effects, such as alteration of smell, nausea, vomiting, or meat aversion. (9)(12)



  • Rapidly absorbed in the upper intestine within one and a half hours (19)
  • Approximately 70% of an absorbed oral dose passes into the blood (6)


  • Passes the blood-brain barrier, unlike serotonin (18)(19)
  • Less freely, tryptophan (5-HTP precursor) can also cross the blood-brain barrier, but this depends on L-type amino acid transporters which are competed for by other amino acids (e.g., tyrosine, valine, phenylalanine, leucine, or isoleucine) (23)
  • Increases intestinal mucosa 5-HTP and serotonin’s primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), but not serotonin itself (25)


  • Decarboxylated to serotonin by the L-aromatic amino acid decarboxylase (AAAD) enzyme (18)(19)
  • Conversion occurs without feedback inhibition, providing the possibility of uninhibited rises in serotonin as solely limited by AAAD (21)
  • Serotonin may be in turn metabolized by monoamine oxidases to 5-HIAA (18)


  • 5-HTP possesses a half-life of two hours (19)
  • Serotonin may be excreted in the urine or as 5-HIAA (33)(37)
  1. Aliño, J. J., Gutierrez, J. L., & Iglesias, M. L. (1976). 5-Hydroxytryptophan (5-HTP) and a MAOI (nialamide) in the treatment of depressions. A double-blind controlled study. International Pharmacopsychiatry, 11(1), 8–15. ()
  2. Angst, J., Woggon, B., & Schoepf, J. (1977). The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Archiv Fur Psychiatrie Und Nervenkrankheiten, 224(2), 175–186. ()
  3. Autret, A., Minz, M., Beillevaire, T., Degos, C., & Cathala, H. P. (1977). Clinical and polygraphic effects of d.1 5 HTP on narcolepsy-cataplexy. Biomedicine, 27(5), 200–203. ()
  4. Battistella, P. A., Bordin, A., Cernetti, R., Broetto, S., Corrà, S., Piva, E., & Plebani, M. (1996). Beta-endorphin in plasma and monocytes in juvenile headache. Headache, 36(2), 91–94. ()
  5. Berger, M., Gray, J. A., & Roth, B. L. (2009). The expanded biology of serotonin. Annual Review of Medicine, 60, 355–366. ()
  6. Birdsall, T. C. (1998). 5-Hydroxytryptophan: A clinically-effective serotonin precursor. Alternative Medicine Review: A Journal of Clinical Therapeutic, 3(4), 271–280. ()
  7. Bruni, O., Ferri, R., Miano, S., & Verrillo, E. (2004). L -5-hydroxytryptophan treatment of sleep terrors in children. European Journal of Pediatrics, 163(7), 402–407. ()
  8. Cangiano, C., Ceci, F., Cairella, M., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M., & Rossi-Fanelli, F. (1991). Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. Advances in Experimental Medicine and Biology, 294, 591–593. ()
  9. Cangiano, C., Ceci, F., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M., Antonucci, F., & Rossi-Fanelli, F. (1992). Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. The American Journal of Clinical Nutrition, 56(5), 863–867. ()
  10. Cangiano, C., Laviano, A., Del Ben, M., Preziosa, I., Angelico, F., Cascino, A., & Rossi-Fanelli, F. (1998). Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 22(7), 648–654. ()
  11. Caruso, I., Sarzi Puttini, P., Cazzola, M., & Azzolini, V. (1990). Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. The Journal of International Medical Research, 18(3), 201–209. ()
  12. Ceci, F., Cangiano, C., Cairella, M., Cascino, A., Del Ben, M., Muscaritoli, M., Sibilia, L., & Rossi Fanelli, F. (1989). The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. Journal of Neural Transmission , 76(2), 109–117. ()
  13. Chen, D., Liu, Y., He, W., Wang, H., & Wang, Z. (2012). Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts. Journal of Huazhong University of Science and Technology. Medical Sciences, 32(3), 422–427. ()
  14. Croonenberghs, J., Spaas, K., Wauters, A., Verkerk, R., Scharpe, S., Deboutte, D., & Maes, M. (2008). Faulty serotonin--DHEA interactions in autism: Results of the 5-hydroxytryptophan challenge test. Neuro Endocrinology Letters, 29(3), 385–390. ()
  15. Croonenberghs, J., Verkerk, R., Scharpe, S., Deboutte, D., & Maes, M. (2005). Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controls. Life Sciences, 76(19), 2171-2183. ()
  16. Cross, D. R., Kellermann, G., McKenzie, L. B., Purvis, K. B., Hill, G. J., & Huisman, H. (2011). A randomized targeted amino acid therapy with behaviourally at-risk adopted children. Child: Care, Health and Development, 37(5), 671–678. ()
  17. De Benedittis, G., & Massei, R. (1985). Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. Journal of Neurosurgical Sciences, 29(3), 239–248. ()
  18. Hinz, M., Stein, A., & Uncini, T. (2012). 5-HTP efficacy and contraindications. Neuropsychiatric Disease and Treatment, 8, 323–328. ()
  19. Jacobsen, J. P. R., Krystal, A. D., Krishnan, K. R. R., & Caron, M. G. (2016). Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: Clinical and preclinical rationale. Trends in Pharmacological Sciences, 37(11), 933–944. ()
  20. Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. K. D. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29–34. ()
  21. Javelle, F., Lampit, A., Bloch, W., Häussermann, P., Johnson, S. L., & Zimmer, P. (2020). Effects of 5-hydroxytryptophan on distinct types of depression: A systematic review and meta-analysis. Nutrition Reviews, 78(1), 77–88. ()
  22. Kahn, R. S., Westenberg, H. G., Verhoeven, W. M., Gispen-de Wied, C. C., & Kamerbeek, W. D. (1987). Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; A double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. International Clinical Psychopharmacology, 2(1), 33–45. ()
  23. Keszthelyi, D., Troost, F. J., Jonkers, D. M., van Eijk, H. M., Dekker, J., Buurman, W. A., & Masclee, A. A. M. (2014). Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome. Alimentary Pharmacology and Therapeutics, 40(4), 392–402. ()
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  34. Rousseau, J. J. (1987). Effects of a levo-5-hydroxytryptophan-dihydroergocristine combination on depression and neuropsychic performance: A double-blind placebo-controlled clinical trial in elderly patients. Clinical Therapeutics, 9(3), 267–272. ()
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