Medically reviewed by Drugs.com. Last updated on July 2, 2020.
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.
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.
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
Oral administration of an extract of G. simplicifolia seeds exerted an anxiolytic effect on rats subjected to dark-light and open field tests.11
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
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
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
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
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
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
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
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
More about 5-HTP (5-hydroxytryptophan)
Related treatment guides
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.