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Medically reviewed by Last updated on July 2, 2020.

Common Name(s): 5-HTP, 5-hydroxytryptophan, Oxitriptan (INN)
Drug class: Herbal products, Miscellaneous antidepressants

Clinical Overview


Clinical trials of 5-HTP conducted in various conditions have resulted in limited evidence suggesting a place in therapy for anxiety, depression, and neurological conditions in which a serotonin deficiency is a contributory factor. 5-HTP may also be an effective appetite suppressant and treatment for opioid withdrawal symptoms, but further clinical trials are needed.


Recent clinical trials do not provide adequate dosing guidelines. Studies in depression have used 5-HTP 200 to 300 mg/day given in 3 to 4 divided doses to prevent possible nausea.


The potential for serotonin syndrome exists with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).


Information regarding safety and efficacy in pregnancy and lactation is lacking.


The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. 5-HTP augments the effect of citalopram and clomipramine, while carbidopa increases the bioavailability of 5-HTP.

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, mild headache, and sleepiness have also been reported.


There is little information on the toxicology of 5-HTP. A possible association with fatal eosinophilia-myalgia syndrome in the 1980s and 1990s has now been attributed to contaminated L-tryptophan.

Scientific Family

  • Caesalpiniaceae
  • Leguminosae


Seeds from the woody climbing shrub G. simplicifolia are used as a source of 5-HTP. The plant can grow to 3 m and is found in tropical Africa, most prevalently in Ghana. It has brown-black branches with simple, large, alternate leaves. The flowers are tubular pale green/orange, and the fruit is an oblique cylindrical black pod, approximately 8 cm long and 4 cm wide, containing the seeds.1


The whole plant is used in African traditional medicine. The pulped bark is used topically on syphilitic sores, and a paste made from the leaves is applied to burns. The leaf sap is used for inflamed eyes, while decoctions made from the stem and leaves are used as a purgative, to relieve constipation, and as a topical antiseptic.

Chewing the stems is said to provide an aphrodisiac effect, and the leaves are regarded as a good food source for animals. The plant is an industrial source of 5-HTP, with Ghana exporting raw materials mostly to Germany.1


The leaves of the plant have a high protein content and contain phosphorus and calcium, as well as a volatile oil, coumarins, and 5-HTP and 5-hydroxytryptamine. The ripe seeds contain as much as 20% 5-HTP and lectins of interest in cancer and neurological research. High-performance liquid chromatography (HPLC) assay methods have been described for the quantification of 5-HTP.1, 2

Uses and Pharmacology

Tryptophan, an essential amino acid, is obtained from animal protein in a Western diet. It is enzymatically converted to 5-HTP by tryptophan hydroxylase, which is further converted to serotonin. Factors that may influence the rate-limiting hydroxylase step in 5-HTP production include stress, insulin resistance, vitamin B6 deficiency, and insufficient magnesium.3, 4 Depleted states of serotonin have been implicated in neurological disorders such as autism, epilepsy, depression, and migraine, among other conditions.4, 5, 6, 7, 8

5-HTP is used by some researchers as a challenge test to examine central serotonergic function, with cortisol and prolactin release used as a measure of response, as well as excretion of the metabolite 5-hydroxy-indoleacetic acid.5, 9, 10


Studies in animals have found both inhibitory effects and heightened aggression with increased serotonin consequent to 5-HTP supplementation. Variables include the animal species used, length of treatment, and type of aggression. Clinical studies are lacking.16

Anxiety/Sleep terrors

Animal data

Oral administration of an extract of G. simplicifolia seeds exerted an anxiolytic effect on rats subjected to dark-light and open field tests.11

Clinical data

Studies in healthy volunteers found that oral administration of 5-HTP reduced the incidence of induced panic and associated symptoms when compared with placebo.12, 13 A gender difference in panic response was suggested in 1 small study.13 A study in children with sleep terrors reported a reduction of more than 50% in incidence with 5-HTP 2 mg/kg/day given at bedtime for 20 days. The effect of 5-HTP persisted in the majority of participants at the 6-month end point.14

Appetite suppression

Studies in rats found decreased food intake and loss of weight with administration of G. simplicifolia extract.17, 18 A small (N = 20) clinical trial evaluated the effect of the extract on satiety among overweight women. Decreased appetite and a decrease in mean body mass index were demonstrated at 4 weeks.19, 20


Animal data

Studies in rodents have demonstrated the effect of 5-HTP on circulating serotonin levels and in sleep deprivation. Additionally, serotonin syndrome can be induced in rats given 5-HTP.4

Clinical data

Approximately 30 clinical trials in depression have been conducted since the 1970s using 5-HTP. Following the occurrence of fatal eosinophilia associated with L-tryptophan and the advent of SSRIs, clinical studies were largely abandoned.3, 4 Of the published clinical studies, 11 were conducted in a double-blind manner. However, the trials used small numbers of participants, and the design of the trials, dosages, and duration were heterogeneous, making a meta-analysis impossible.4 Larger, more robust clinical trials are warranted to determine a place for 5-HTP in the management of depression.3, 4 A more recent exploratory study in healthy volunteers suggests a role for 5-HTP in the short-term setting while waiting for the onset of action of an SSRI.15

A randomized, double-blind comparator trial in 60 patients in India with first episode depression found no statistically significant difference in treatment response between groups treated with 5-HTP compared to fluoxetine. In this 8-week study, 5-HTP and fluoxetine were titrated up to 400 mg/day and 40 mg/day, respectively, over 4 weeks. Improvement in HAM-D scores from baseline were significant in both groups resulting in an approximate 58% and 64% reduction in scores at 8 weeks for 5-HTP and fluoxetine, respectively, that included a positive response (more than 50% reduction from baseline) from a respective 73% and 80% of patients. No significant difference was observed in adverse effects between groups. Nausea, anorexia, and headache were the most commonly reported effects in both groups with insomnia also common with fluoxetine.32


Limited clinical studies were conducted in the 1980s. A more recent clinical trial found no effect of 5-HTP 300 mg/day on the number of tension-type (nonmigraine) headaches experienced during the 8-week study. However, in the 2-week period after treatment was stopped, a decrease in number of days with headache was observed. A difference over placebo was found for consumption of analgesics.21

Irritable bowel syndrome

The effect of 5-HTP on short-term modulation of the small intestinal barrier was investigated in a small double-blind, randomized, placebo-controlled crossover trial (n=30). One hour after oral administration of 5-HTP 100 mg or placebo, both healthy and irritable bowel syndrome (IBS) patients received a 1.5 g sugar challenge. 5-HTP supplementation resulted in significantly higher mucosal turnover of serotonin in IBS patients compared to healthy controls (P=0.005). Gene transcription of the tight junction protein occludin was found to be significantly lower in IBS patients irrespective of administration of 5-HTP (P=0.001) or placebo (P=0.006). Overall, oral 5-HTP administration resulted in pronounced alterations in mucosal serotonin metabolism in IBS patients but without reinforcement of the intestinal barrier function that was observed in healthy controls. Participants receiving 5-HTP experienced abdominal pain (n=3), bloating (n=1), and diarrhea (n=1); no side effects were experienced in the placebo group.28


A clinical trial evaluated the efficacy of 5-HTP 150 mg daily in the frequency of hot flashes, finding no difference over placebo.22

Neurological diseases

Reviews of studies using 5-HTP in degenerative ataxia and pediatric neurotransmitter diseases suggest a potential role in reducing neurological symptoms; however, inconsistent findings have been reported.7, 8 Measurement of executive control was found to be significantly reduced by a single oral dose of 5-HTP 150 mg compared to placebo in healthy volunteers enrolled in a double-blind, randomized controlled trial (n=66). The testing method used indicated that exogenous 5-HTP effected forebrain dopamine synthesis, thereby reducing execution time to complete tasks.29

Opioid withdrawal

Continual nocturnal muscle spasms secondary to opioid withdrawal in a 53-year-old female were relieved with 5-HTP supplementation initiated at 200 mg and followed by 100 mg nightly until symptom improvement. The patient was intolerant to the side effects of clonidine, the cornerstone and only non-opioid treatment for opioid weaning.30


Studies in depression have used dosages varying from 20 to 3,250 mg daily; however, most commonly 200 to 300 mg/day has been used.3, 4 5-HTP has a short half-life, and 3 to 4 divided doses are recommended to reduce the likelihood of nausea.4, 9, 32

Studies have been conducted in children (range, 3 to 17 years of age).5, 14, 23 Because 100 mg given twice a day caused agitation in 20% of the participants (behaviorally at-risk children), the dosage was reduced to 100 mg/day.23

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.3 5-HTP has been shown to increase luteinizing hormone secretion in women, possibly via an increase in gonadotropin-releasing hormone.24


The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. Reports exist of serotonin syndrome consequent to L-tryptophan and fluoxetine combinations, but no reports to date can be attributed to 5-HTP.3 Studies have shown 5-HTP to augment the effect of citalopram and clomipramine.15 Carbidopa increases the bioavailability of 5-HTP.25

5-HTP has been shown to increase the urinary levels of 5-hydroxyindoleacetic acid, a marker for carcinoid tumor, which may lead to misinterpretation of laboratory tests.26, 31

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, bloating, mild headache, anorexia, and sleepiness have also been reported.3, 15, 28, 32

Laboratory studies in rats have demonstrated a suppressive effect on sexual behavior with short-term doses of G. simplicifolia extract in both males and females; however, no effect was observed with dosing of up to 9 days' duration and clinical importance of this is unclear.17, 18


Information regarding the toxicology of 5-HTP is lacking. A possible association with fatal eosinophilia-myalgia syndrome noted in the 1980s and 1990s has now been attributed to contaminated L-tryptophan.3, 4, 23, 27 HPLC identification of the implicated contaminant tryptophan-4,5-dione (referred to in publications as "Peak X") has also been disputed in a review of the safety of 5-HTP, but remains a requirement of the US Food and Drug Administration for all commercial 5-HTP products.27 Rats fed 5-HTP for a year showed no toxicological effects, and no reports of human toxicity have been documented since the mid-1990s.27


1. Bosch, CH, Griffonia simplicifolia (Vahl ex DC.) Baill. In: Schmelzer GH, Gurib-Fakim A, eds. Medicinal plants/Plantes médicinales 1 [CD-ROM]. Prota 11(1). Wageningen, Netherlands: PROTA; 2008.
2. Lemaire PA, Adosraku RK. An HPLC method for the direct assay of the serotonin precursor, 5-hydroxytrophan, in seeds of Griffonia simplicifolia. Phytochem Anal. 2002;13(6):333-337.12494751
3. Iovieno N, Dalton ED, Fava M, Mischoulon D. Second-tier natural antidepressants: review and critique. J Affect Disord. 2011;130(3):343-357.20579741
4. Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006;109(3):325-338.16023217
5. Croonenberghs J, Verkerk R, Scharpe S, Deboutte D, Maes M. 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 Sci. 2005;76(19):2171-2183.15733932
6. Bagdy G, Kecskemeti V, Riba P, Jakus R. Serotonin and epilepsy [published online ahead of print January 24, 2007]. J Neurochem. 2007;100(4):857-873.17212700
7. Pons R. The phenotypic spectrum of paediatric neurotransmitter diseases and infantile parkinsonism. J Inherit Metab Dis. 2009;32(3):321-332.19107571
8. Trujillo-Martín MM, Serrano-Aguilar P, Monton-Alvarez F, Carrillo-Fumero R. Effectiveness and safety of treatments for degenerative ataxias: a systematic review. Mov Disord. 2009;24(8):1111-1124.19412936
9. Gijsman HJ, van Gerven JM, de Kam ML, et al. Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers. J Clin Psychopharmacol. 2002;22(2):183-189.11910264
10. Schruers K, van Diest R, Nicolson N, Griez E. L-5-hydroxytryptophan induced increase in salivary cortisol in panic disorder patients and healthy volunteers. Psychopharmacology (Berl). 2002;161(4):365-369.12073163
11. Carnevale G, Di Viesti V, Zavatti M, Zanoli P. Anxiolytic-like effect of Griffonia simplicifolia Baill. seed extract in rats. Phytomedicine. 2011;18(10):848-851.21353511
12. Schruers K, van Diest R, Overbeek T, Griez E. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. 2002;113(3):237-243.12559480
13. Maron E, Toru I, Vasar V, Shlik J. The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. J Psychopharmacol. 2004;18(2):194-199.15260907
14. Bruni O, Ferri R, Miano S, Verrillo E. L-5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr. 2004;163(7):402-407.15146330
15. Lowe SL, Yeo KP, Teng L, et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006;31(4):473-484.16378695
16. Carrillo M, Ricci LA, Coppersmith GA, Melloni RH Jr. The effect of increased serotonergic neurotransmission on aggression: a critical meta-analytical review of preclinical studies. Psychopharmacology (Berl). 2009;205(3):349-368.19404614
17. Carnevale G, Di Viesti V, Zavatti M, Benelli A, Zanoli P. Influence of Griffonia simplicifolia on male sexual behavior in rats: behavioral and neurochemical study. Phytomedicine. 2011;18(11):947-952.21641194
18. Carnevale G, Di Viesti V, Zavatti M, Benelli A, Zanoli P. Griffonia simplicifolia negatively affects sexual behavior in female rats. Phytomedicine. 2010;17(12):987-991.20359873
19. Rondanelli M, Opizzi A, Faliva M, Bucci M, Perna S. Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration [published online ahead of print May 12, 2011]. Eat Weight Disord.22142813
20. Rondanelli M, Klersy C, Iadarola P, Monteferrario F, Opizzi A. Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation. Int J Obes (Lond). 2009;33(10):1174-1182.19752879
21. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Headache. 2000;40(6):451-456.10849040
22. Freedman RR. Treatment of menopausal hot flashes with 5-hydroxytryptophan. Maturitas. 2010;65(4):383-385.20031347
23. Cross DR, Kellermann G, McKenzie LB, Purvis KB, Hill GJ, Huisman H. A randomized targeted amino acid therapy with behaviourally at-risk adopted children. Child Care Health Dev. 2011;37(5):671-678.21166834
24. Lado-Abeal J, Graña M, Rey C, Cabezas-Cerrato J. L-5-hydroxytryptophan does not stimulate LH secretion directly from the pituitary in patients with gonadotrophin releasing hormone deficiency. Clin Endocrinol (Oxf). 1998;49(2):203-207.9828908
25. Smarius LJ, Jacobs GE, Hoeberechts-Lefrandt DH, et al. Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa. J Psychopharmacol. 2008;22(4):426-433.18308795
26. Joy T, Walsh G, Tokmakejian S, Van Uum SH. Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake. Can J Gastroenterol. 2008;22(1):49-53.18209781
27. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150(1):111-122.15068828
28. Keszthelyi D, Troost FJ, Jonkers DM, et al. Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome. Aliment Pharmacol Ther. 2014;40(4):392-402.24943480
29. Gendle MH, Young EL, Romano AC. Effects of oral 5-hydroxytryptophan on a standardized planning task: insight into possible dopamine/serotonin interactions in the forebrain. Hum Psychopharmacol. 2013;28(3):270-273.23609610
30. Dais J, Khosia A, Doulatram G. The successful treatment of opioid withdrawal-Induced refractory muscle spasms with 5-HTP in a patient intolerant to clonidine. Pain Physician. 2015;18(3):E417-E420.26000689
31. Hallin ML, Mahmoud K, Viswanath A, Gama R. 'Sweet Dreams', 'Happy Days' and elevated 24-h urine 5-hydroxyindoleacetic acid excretion. Ann Clin Biochem. 2013;50(Pt 1):80-82.23086978
32. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. 2013;6(1):29-34.23380314


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