Drugs A - Z
5-HTP (5-Hydroxytryptophan, L-5-Hydroxytryptophan)
Generic Name: 5-hydroxytryptophan
CategoryHerbs & Supplements
5-Hydroxytroptophan, Griffonia simplicifolia, L-5-HTP, L-5-Hydroxytroptophan, oxitriptan, Tript-OH®, tryptophan.
Note: Not to be confused with L-tryptophan.
5-HTP is the precursor of the neurotransmitter serotonin. It is obtained commercially from the seeds of the plant Griffonia simplicifolia.
5-HTP has been suggested as a treatment for many conditions. There is some research to support the use of 5-HTP in treating cerebellar ataxia, headache, depression, psychiatric disorders, fibromyalgia, and as an appetite suppressant or weight-loss agent. There is not enough scientific evidence to support the use of 5-HTP for any other medical condition.
5-HTP may cause gastrointestinal disturbances, mood disturbances, seizure, or abnormal blood counts. Some reported side effects might result from contaminants in 5-HTP products.
EvidenceDISCLAIMER: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Cerebellar ataxia :
Cerebellar ataxia results from the failure of part of the brain to regulate body posture and limb movements. 5-HTP has been observed to have benefits in some people who have difficulty standing or walking because of cerebellar ataxia. However, current evidence is mixed.
The results of numerous studies in humans suggest that 5-HTP may aid in the treatment of depression. However, it is not known whether 5-HTP is as effective as commonly prescribed antidepressant drugs.
There is a small amount of research evaluating the use of 5-HTP for fibromyalgia, and early evidence suggests that 5-HTP may reduce the number of tender points, anxiety, and intensity of pain and may improve sleep, fatigue, and morning stiffness.
There is evidence from several studies in both children and adults that 5-HTP may be effective in reducing the severity and frequency of headaches, including tension headaches and migraines. Further research is needed.
Studies suggest that 5-HTP may reduce eating behaviors, lessen caloric intake, and promote weight loss in obese individuals.
Alcoholism (withdrawal symptoms):
Early study suggests that 5-HTP may lessen alcohol withdrawal symptoms. Further research is needed to confirm these results.
Although 5-HTP has been proposed as a possible treatment for anxiety disorders, there is not enough human evidence to make a firm recommendation.
Preliminary study of 5-HTP in children with Down's syndrome yields insignificant results. Further research is necessary.
Neurologic disorders (Lesch-Nyhan syndrome):
Lesch-Nyhan syndrome (LNS) is a rare, genetic disorder affecting mostly males that often causes mental retardation and self-mutilation. Small studies of 5-HTP in Lesch-Nyhand syndrome show conflicting results. Additional study is needed.
It has been suggested that 5-HTP may reduce psychotic symptoms and mania or aid in panic disorder, but studies in people with schizophrenia have shown differing results.
There is insufficient evidence regarding the use of 5-HTP for sleep disorders. Additional studies are needed before a conclusion can be drawn.
Seizures/epilepsy (myoclonic disorders):
Although 5-HTP has been studied as a treatment for various myoclonic syndromes and epilepsy, available research does not support the use of 5-HTP for these conditions.
TraditionWARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Aggression, agoraphobia (fear of open/public spaces), Alzheimer's disease, amyotrophic lateral sclerosis (fatal progressive neurological disease), anorexia, attention deficit hyperactivity disorder (ADHD), autism, bipolar disorder, bulimia nervosa, cough, deficiency (aromatic L-amino acid decarboxylase deficiency; serotonin deficiency), delirium tremens (DTs), diabetes, digestion, dizziness, dystonia (muscle spasms), eating disorders (binge eating), endocrine disorders (Cushing's syndrome), eye disorders (ophthalmoplegia), hepatitis, herpes virus infection (Ramsey-Hunt's syndrome), hormonal disorders, inflammation, insomnia, menopausal symptoms, mood disorder, myoclonic disorders (Lance-Adams syndrome), obsessive compulsive disorder (OCD), pain, panic disorder, Parkinson's disease, phenylketonuria, premenstrual syndrome (PMS), psychosis (LSD-induced), restless leg syndrome, seasonal affective disorder, sexual dysfunction, temperature regulation.
Adults (18 years and older)
In general, most studies have administered 5-HTP at low doses and for a short duration. A common dose used is 300 milligrams per day, which has been taken for depression or headache. Doses as high as 1,600 milligrams per day or 16 milligrams per kilogram per day over 12 months have been studied. Starting with low doses (50 milligrams three times daily) and increasing the dosage gradually may minimize side effects such as nausea.
Children (younger than 18 years)
There is not enough scientific data to recommend 5-HTP for use in children, and 5-HTP is not usually recommended because of potential side effects. However, for headache, 100 milligrams daily for 12 weeks has been used.
SafetyDISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.
Side Effects and Warnings
Although 5-HTP appears to be generally well tolerated, due to potential serious adverse effects, a physician should supervise the use of 5-HTP. Cases of eosinophilia myalgia syndrome (EMS) have been reported and although the precise role of 5-HTP in these cases remains unclear, it has been suggested that contaminants in certain batches were responsible for these adverse effects. Several thousand cases of EMS and deaths were linked to the ingestion of contaminated L-tryptophan in 1989. Avoid in patients with eosinophilia syndromes.
Palpitations, lowered blood pressure, myalgia (muscle pain), weakness, rhabdomyolysis (breakdown of skeletal muscle), eosinophilia (increased number of white blood cells), nausea, vomiting, abdominal pain, heartburn, diarrhea, gas, and taste alteration have been reported. Slow initiation of treatment and enteric-coated tablets has decreased gastrointestinal side effects.
Drowsiness, dizziness, vertigo, somnolence (sleepiness), insomnia, and headache are occasionally reported. Mania and euphoria have also been noted. Seizure syndrome has occurred in patients with Down's syndrome. Despite possible efficacy of 5-HTP for Down's syndrome, 5-HTP is not recommended in Down's syndrome patients.
Other potential side effects of taking 5-HTP by mouth may include transient disinhibition, euphoria, irritability, depressed mood, restlessness, rapid speech, anxiety, aggressiveness, and agitation. Weight gain has been reported in a few cases. In contrast, loss of appretite has also been reported. Amenorrhea (absence of menstruation) was noted in one case.
Patients receiving both carbidopa (a drug for Parkinson's disease) and 5-HTP long-term had reductions in total cholesterol, bradycardia (slowed heart rate), hypomania (mild mania), pseudobullous morphea (chronic, degenerative disease that affects the joints, skin, and internal organs), and scleroderma-like illness.
An intravenous derivative of 5-HTP called gamma-L-glutamyl 5-HTP administered over one hour resulted in sodium retention. It is unknown if this effects was the result of the formulation, the route of administration, or the rate of infusion.
Use cautiously in patients with kidney insufficiency, as 5-HTP is eliminated through the kidneys.
Pregnancy and Breastfeeding
5-HTP is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence. The risk of contaminants found in 5-HTP products further precludes use during pregnancy. 5-HTP may increase prolactin, a necessary hormone for milk production; 5-HTP should be avoided while breastfeeding.
Interactions with Drugs
When 5-HTP is used with drugs that act within the central nervous system, there may be an increased risk of adverse effects. Examples of such drugs include carbidopa, fluoxetine (Prozac®), buspirone (Buspar®), phenelzine (Nardil®), amitriptyline (Elavil®), phenobarbital, trazodone (Desyrel®), venlafaxine (Effexor®), tramadol (Ultram®), sumatriptan (Imitrex®), mirtazapine (Remeron®), and pindolol. If a patient experiences muscle aches, fever, or other abnormalities when taking 5-HTP with other drugs, a healthcare professional should be notified immediately. In contrast, drugs such as methysergide or cyproheptadine may reduce the effects of 5-HTP.
5-HTP may enhance the serotonergic effect of selective serotonin reuptake inhibitors (SSRIs). Since 5-HTP increases serotonin levels, when combined with an SSRI, the serotonin level may be increased sufficiently to produce serotonin syndrome. Anecdotally, zolpidem has been associated with exacerbating hallucinations when taken with SSRIs. Its use with 5-HTP may result in a similar effect. Serotonin receptor antagonists, such as methysergide and cyproheptadine, may diminish efficacy of 5-HTP.
Concomitant use of serotonin specific reuptake inhibitors and monoamine oxidase inhibitors (MAOIs) can cause serotonin syndrome. The addition of 5-HTP may potentiate the antidepressant effect of MAOIs and decrease time to recovery from depression.
Losartan® (angiotensin receptor blocker) may cause a decrease in pineal serotonin levels.
Administration of 5-HTP with decarboxylase inhibitors can increase the plasma concentration and half-life of 5-HTP.
5-HTP, when taken with fenfluramine, may cause suppression in food intake.
The 5-HTP-induced increase in plasma cortisol can be blocked by the administration of ritanserin, a 5-HT2/5-HT1C antagonist.
Although human evidence is lacking, 5-HTP may interact with angiotensin II receptor antagonist (A2R blockers) and thyroid stimulating hormones. 5-HTP has also been shown to increase luteinizing hormone, although the effects on hormones in humans are unclear.
5-HTP has produced weight loss in the obese. In theory, 5-htp may interact additively or synergistically with other weight loss agents. Furthermore, based on animal study, 5-HTP may improve locomotor function and survival in ALS patients when taken with riluzole.
5-HTP may alter the concentrations of certain agents metabolized by the liver or interact with agents eliminated through the kidneys
Interactions with Herbs and Dietary Supplements
In theory, L-tyrosine, adenosyl-L-methionine, tryptophan, vitamin B6, chromium, melatonin, niacin, SAMe, St. John's wort, herbs and supplements with monoamine oxidase inhibitor (MAOI) activity, and magnesium may increase the effects or side effects associated with 5-HTP.
Although human evidence is lacking, 5-HTP may interact with herbs or supplements with proposed antidepressant effects or thyroid stimulating effects. 5-HTP has also been shown to increase luteinizing hormone, although the effects on hormones in humans are unclear.
When 5-HTP is used with agents that act within the central nervous system, there may be an increased risk of adverse effects. In theory, use with St. John's wort may increase serotonin levels, resulting in adverse effects, including serotonin syndrome.
In theory, 5-HTP may have additive effects with sedatives or agents taken for epilepsy or seizures. 5-HTP has produced weight loss in the obese. In theory, 5-HTP may interact additively or synergistically with other weight loss agents.
It has been suggested that 5-HTP may reduce psychotic symptoms and mania or aid in panic disorder, but studies in people with schizophrenia have shown different results. Caution is advised.
5-HTP may alter the concentrations of certain agents metabolized by the liver or interact with agents eliminated through the kidneys
Authors/Editors: Tracee Abrams, PharmD (University of Rhode Island); Heather Boon, BScPhm, PhD (University of Toronto); Robert D'Alessandro, MS (Northeastern University); Nicole Giese, MS (Natural Standard Research Collaboration); Michael Goble, BS, PharmD (Massachusetts College of Pharmacy); Dana Hackman, BS (Northeastern University); Paul Hammerness, MD (Harvard Medical School); Sadaf Hashmi, MD, MPh (Johns Hopkins School of Hygiene and Public Health); Lisa Scully, PharmD (Massachusetts College of Pharmacy); Erica Seamon, PharmD (Nova Southeastern University); Michael Smith, MRPharmS, ND (Canadian College of Naturopathic Medicine); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Candy Tsourounis, PharmD (University of California); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Mamta Vora, PharmD (Natural Standard Research Collaboration); Wendy Weissner, BA (Natural Standard Research Collaboration).
BibliographyDISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr 10-11-1977;224(2):175-186.
Bagdy G, Kecskemeti V, Riba P, et al. Serotonin and epilepsy. J Neurochem 2007;100(4):857-873.
Belongia EA, Hedberg CW, Gleich GJ, et al. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. The New England Journal of Medicine 8-9-1990;323(6):357-365.
Birdsall, T. C. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev 1998;3(4):271-280.
Bono G, Micieli G, Sances, G, et al. L-5HTP treatment in primary headaches: an attempt at clinical identification of responsive patients. Cephalalgia 1984;4(3):159-165.
Caruso I, Sarzi Puttini P, Cazzola M, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990;18(3):201-209.
De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study--L-5-HTP versus placebo. Drugs Exp Clin Res. 1987;13(7):425-433.
Eriksson O, Wall A, Marteinsdottir I, et al. Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Psychiatry Res 3-31-2006;146(2):107-116.
Halford JC, Harrold JA, Boyland EJ, et al. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Drugs 2007;67(1):27-55.
Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24(2):53-81.
Puttini PS, Caruso I. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res 1992;20(2):182-189.
Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;(1):CD003198.
Thomson J, Rankin H, Ashcroft GW, et al. The treatment of depression in general practice: a comparison of L- tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. Psychol Med 1982;12(4):741-751.
Titus F, Davalos A, Alom J, et al. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25(5):327-329.
Trouillas P, Brudon F, Adeleine P. Improvement of cerebellar ataxia with levorotatory form of 5- hydroxytryptophan. A double-blind study with quantified data processing. Arch.Neurol 1988;45(11):1217-1222.