5-HTP is produced from the seeds of the African plant Griffonia simplicifolia. It is used for sleep disorders, depression, anxiety, migraine and tension-type headaches, fibromyalgia, binge eating associated with obesity, attention deficit disorder (ADD), and as adjunctive therapy in seizure disorder and Parkinson's disease. Taking 5-HTP seems to significantly improve symptoms of depression, including in patients with treatment-resistant depression. There is evidence that 5-HTP might be comparable to the conventional antidepressants fluvoxamine and imipramine (Tofranil). 5-HTP appears to improve symptoms of fibromyalgia, including pain severity, morning stiffness and sleeplessness.
Published Clinical Studiescltop
1
The serotonin precursor 5-hydroxytryptophan delays neuromuscular disease in murine familial amyotrophic lateral sclerosis.
Turner BJ, Lopes EC, Cheema SS.
Neurodegeneration Research Laboratory, Department of Anatomy and Cell Biology, Monash University, Victoria, Australia.
INTRODUCTION: Reduction in the levels of whole-blood serotonin is a common feature of Down syndrome (DS) individuals and transgenic mice overexpressing wild-type SOD1. Administration of the metabolic precursor 5-hydroxytryptophan (5-HTP) leads to reversal of both serotonin deficits and hypotonia in humans. The effect of 5-HTP treatment on the progression of motor neuron disease in mutant SOD1 mice was examined. METHODS: Pre-disease transgenic SOD1 G93A mice and wild-type littermates were systemically administered 5-HTP thrice weekly (0, 5 or 50 mg/kg). Animal weights, locomotor function and survival were recorded weekly. Plasma serotonin levels were measured post-mortem. RESULTS: Treatment with 5-HTP significantly delayed hindlimb weakness and mortality in SOD1 G93A mice in a dose-dependent manner. Wild-type mice were not adversely affected by 5-HTP administration. Baseline serotonin levels did not differ between wild-type and ALS mice. Blood platelet serotonin levels increased proportionally with dose. CONCLUSIONS: Increased blood serotonin by administration of 5-HTP in SOD1 G93A mice led to improved locomotor function and survival. A role for serotonin metabolism in mice with elevated SOD1 expression and motor neuron disease is suggested by these studies.
PMID: 14527871 [PubMed - indexed for MEDLINE]
2
Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients.
Schruers K, van Diest R, Overbeek T, Griez E.
Department of Psychiatry and Neuropsychology, Institute of Brain and Behaviour, Maastricht University, P.O. Box 88, The Netherlands. koen.schruers@pn.unimaas.nl
Previous research showed that lowering the availability of serotonin to the brain by tryptophan depletion increases the vulnerability of panic disorder patients for an experimental 35% CO(2) panic challenge. The results also suggested that increased availability of serotonin inhibits the response to such a challenge. In the present study, this latter possibility is examined. The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% CO(2) panic challenge was assessed following administration of 200-mg L-5-hydroxytryptophan (the immediate precursor of serotonin) or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.
Publication Types:
PMID: 12559480 [PubMed - indexed for MEDLINE]
The safety of triptans in the treatment of patients with migraine.3
Jamieson DG.
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in the past decade has brought migraine-specific pain relief to those suffering from migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on cerebral vessels. Concerns about their safety, particularly in patients with vascular risk factors, have been raised because triptans also activate the 5-HT(1B) receptors on coronary arteries. Although triptans are contraindicated in patients with cardiac or cerebrovascular disease, they are safer than many other medications used to treat patients with migraine, including the nonspecific serotonin-agonist ergot preparations.
Publication Types:
PMID: 11835952 [PubMed - indexed for MEDLINE]
4
The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy.
Moret C, Briley M.
NeuroBiz BioConsulting, Les Grezes, La Verdarie, 81100, Castres, France.
Serotonin (5-hydroxytryptamine, 5-HT) is implicated in several psychiatric diseases. Is this also true for 5-HT(1B/D) receptors? These receptors are found in high density in substantia nigra, globus pallidus, striatum and basal ganglia and in other brain regions. This ubiquity makes 5-HT(1B/D) receptors responsible for many physiological and behavioural functions. This review focuses on the role of 5-HT(1B) receptors in the regulation of 5-HT release and synthesis. Microdialysis experiments performed on freely moving animals are an interesting in vivo model to study the function of the terminal 5-HT(1B) autoreceptor. Synthesis of 5-HT, estimated by the measurement of the accumulation of 5-hydroxytryptophan (5-HTP) ex vivo or in vitro, is modulated by the 5-HT(1B) autoreceptors. Many reports have shown that chronic administration with selective serotonin reuptake inhibitors leads to the desensitisation of the terminal 5-HT(1B) autoreceptors. With the help of some animal models of depression and anxiety and with some data from clinical studies it has been hypothesised that 5-HT(1B) receptors may be supersensitive in depression, anxiety and obsessive compulsive disorder. Thus, since the dysfunction of 5-HT(1B) receptors may be involved in some pathological states, particularly in the psychiatric field, these receptors represent important potential targets for drugs to treat mental diseases.
Publication Types:
PMID: 10980257 [PubMed - indexed for MEDLINE]
Use of neurotransmitter precursors for treatment of depression.5
Meyers S.
Lawrence Berkeley National Laboratory, Berkeley, CA, USA. spmeyers@lbl.gov
Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today. In the late 1970s and 1980s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-tryptophan and 5-hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors tyrosine and L-phenylalanine. This article briefly reviews the published research on the efficacy of neurotransmitter precursors in treating depression, highlights the findings of studies, and discusses issues regarding the interpretation of those findings. The nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression. While there is evidence that precursor loading may be of therapeutic value, particularly for the serotonin precursors 5-HTP and tryptophan, more studies of suitable design and size might lead to more conclusive results. However, the evidence suggests neurotransmitter precursors can be helpful in patients with mild or moderate depression.
Publication Types:
PMID: 10696120 [PubMed - indexed for MEDLINE]
Fibromyalgia and the serotonin pathway.6
Juhl JH.
Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.
Publication Types:
PMID: 9802912 [PubMed - indexed for MEDLINE]
5-Hydroxytryptophan: a clinically-effective serotonin precursor.7
Birdsall TC.
73541.2166@compuserve.com
5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.
Publication Types:
PMID: 9727088 [PubMed - indexed for MEDLINE]
8
Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.
Birmaher B, Kaufman J, Brent DA, Dahl RE, Perel JM, al-Shabbout M, Nelson B, Stull S, Rao U, Waterman GS, Williamson DE, Ryan ND.
University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pa., USA.
BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.
PMID: 9400347 [PubMed - indexed for MEDLINE]
In search of the mode of action of antidepressants: 5-HTP/tyrosine mixtures in depression.9
van Praag HM.
For a long time, antidepressants have been considered to act via enhancement of central MA-ergic activity (due to reuptake or MAO inhibition). An alternative hypothesis holds that their action is based on down-regulation of MA-ergic activity (due to decrease in density or sensitivity of certain receptor populations). In this chapter I have discussed the likelihood of both hypotheses and have reached the conclusion that the first one is the more plausible. I have discussed the following arguments: The 5-HT precursor 5-HTP, which is transformed to 5-HT in the brain, has antidepressant properties. There are indications that the same holds true for tyrosine, a CA precursor transformed in the brain to DA and NE. I found evidence that the 5-HTP effects in depression are potentiated by tyrosine. Since activation rather than suppression of MA-ergic activity seems to be linked to antidepressant activity, it seems likely that the signs of decreased MA metabolism that has been demonstrated in certain types of depression are the expression of a primary metabolic deficit rather than a phenomenon secondary to receptor hyper-sensitivity. Further clinical studies of 5-HT/CA precursor combinations in depression are justified.
Publication Types:
PMID: 6380226 [PubMed - indexed for MEDLINE]
10
Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.
Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V.
Rheumatology Unit, L. Sacco Hospital, Milan, Italy.
A double-blind, placebo-controlled study of the efficacy and tolerability of 5-hydroxytryptophan (5-HTP) was conducted in 50 patients with primary fibromyalgia syndrome. All the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported. Further controlled studies are required to define properly the value of 5-HTP in patients with primary fibromyalgia syndrome.
Publication Types:
PMID: 2193835 [PubMed - indexed for MEDLINE]
L-5-hydroxytryptophan in the treatment of anxiety disorders.11
Kahn RS, Westenberg HG.
Ten outpatients suffering from anxiety states (Anxiety Disorders: DSM-III) were treated with L-5-hydroxytryptophan and carbidopa. A significant reduction in anxiety was observed on three different anxiety scales. It is suggested that 5-HT systems may be involved in the mediation of anxiety.
PMID: 3157732 [PubMed - indexed for MEDLINE]