Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels. However, several studies have reported that 5-HTP is effective even without a peripheral decarboxylase inhibitor (e.g. carbidopa). Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa.
Though 5-HTP is found in food only in insignificant quantities, it is a chemical involved intermediately in the metabolism of tryptophan, an amino acid found in milk, meat, potatoes, pumpkin, and various greens. See also the Dietary sources section of the article on L-tryptophan.
In 2001 a Cochrane Review of the effect of 5-HTP and tryptophan on depression was published. The authors included only studies of a high rigor and included both 5-HTP and tryptophan in their review because of the limited data on either. Of 108 studies of 5-HTP and tryptophan on depression published between 1966 and 2000, only two met the authors' quality standards for inclusion, totaling 64 study participants. The substances were more effective than placebo in the two studies included but the authors state that, "the evidence was of insufficient quality to be conclusive," and note, "because alternative antidepressants exist which have been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan is limited at present."
5-HTP is often taken by people coming down from MDMA to relieve post-MDMA dysphoria. The basis for doing this is that 5-HTP is a necessary precursor for the brain to produce more serotonin, and MDMA use depletes a person's natural serotonin levels, thus taking 5-HTP after consuming MDMA is speculated as helping improve serotonin production. While the practice is common, the theory is physiologically reasonable, and anecdotal evidence is widespread, no scientifically verifiable evidence can currently be found to confirm whether the practice actually works. No conclusive evidence suggests coadministration of 5-HTP and serotonin releasing agents such as MDMA carry increased risk of serotonin syndrome, and anecdotal evidence suggests coadministration may decrease some of the neurotoxic metabolites produced as degradation products of MDMA (see Alpha-Methyldopamine)
Possible risks or side effects
Because 5-HTP has not been thoroughly studied in a clinical setting, possible side effects and interactions with other drugs are not well known. However, it is noteworthy that no published reports of serious side effects (from non-contaminated 5-HTP) exist, despite that 5-HTP is freely available as a nutraceutical. This could indicate that serious side effects are relatively rare with 5-HTP, at least in moderate doses[quantify]. On the other hand, acute moderate gastrointestinal effects, such as diarrhea and vomiting, are common upon administration of 5-HTP, probably due to rapid formation of serotonin in the upper intestinal tract.
Oral 5-HTP results in an increase in urinary 5-HIAA, a serotonin metabolite, indicating that 5-HTP is peripherally metabolized to serotonin, which is then metabolized. This might cause a false positive test in tests looking for carcinoid syndrome.
In humans 5-HTP has never been clinically associated with serotonin syndrome. Due to the rate-limiting nature of the decarboxylase enzyme which converts 5-HTP into serotonin, the risk of serotonin syndrome with monoamine oxidase inhibitors is thought to be quite low unless both MAOIs and 5-HTP are taken in large quantities.
When combined with carbidopa (as a treatment for symptoms of Parkinson's disease), 5-HTP causes nausea and vomiting; however this can be alleviated via administration of granisetron. As mentioned above under pharmacology, cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP.
It has been suggested by the pharmaceutical industry that 5-HTP may cause eosinophilia-myalgia syndrome (EMS), a serious condition which results in extreme muscle tenderness, myalgia, and blood abnormalities. However, there is evidence to show that EMS was caused by a contaminant in early 5-HTP supplements, before the introduction of the current Good Manufacturing Practices by the United States FDA in 2007. Many countries now employ similar regulation.
^ abShaw K, Turner J, Del Mar C (2002). Shaw, Kelly A, ed. "Tryptophan and 5-hydroxytryptophan for depression". Cochrane Database of Systematic Reviews (Online) (1): CD003198. doi:10.1002/14651858.CD003198. PMID11869656.
^Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M (1982). "Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats". Jpn. J. Pharmacol.32 (5): 803–11. doi:10.1254/jjp.32.803. PMID6983619.
^Bouchard, S; Bousquet, C; Roberge, AG (1981). "Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat". Journal of Neurochemistry37 (3): 781–7. doi:10.1111/j.1471-4159.1982.tb12555.x. PMID6974228.
^Gomes P, Soares-da-Silva P. (1999). "L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4". Brain Res.829 (1–2): 143–150. doi:10.1016/S0006-8993(99)01387-6. PMID18445233.
^Bouchard S, Roberge AG (1979). "Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat". Can. J. Biochem.57 (7): 1014–8. doi:10.1139/o79-126. PMID39668.
^Amamoto T, Sarai K (1976). "On the tryptophan-serotonin metabolism in manic-depressive disorders. Changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression". Hiroshima J. Med. Sci.25 (2–3): 135–40. PMID1088369.
^Magnussen I, Jensen TS, Rand JH, Van Woert MH (1981). "Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man". Acta pharmacologica et toxicologica49 (3): 184–9. doi:10.1111/j.1600-0773.1981.tb00890.x. PMID6175178.
^Birdsall TC (1998). "5-Hydroxytryptophan: a clinically-effective serotonin precursor". Alternative medicine review : a journal of clinical therapeutic3 (4): 271–80. PMID9727088.
^Sternberg EM, Van Woert MH, Young SN, et al. (1980). "Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa". N. Engl. J. Med.303 (14): 782–7. doi:10.1056/NEJM198010023031403. PMID6997735.
^ abTurner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006 Mar;109(3):325-38. Epub 2005 Jul 14. Review. PubMed PMID 16023217.
^Byerley WF, Judd LL, Reimherr FW, Grosser BI. 5-Hydroxytryptophan: a review of its antidepressant efficiency and adverse effects. J Clin Psychopharmacol. 1987 Jun;7(3):127-37. Review. PubMed PMID 3298325.
^van Hiele LJ. l-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with 'therapy-resistant' depressions. Neuropsychobiology. 1980;6(4):230-40. PubMed PMID 6967194.
^Gijsman HJ, van Gerven JM, de Kam ML, Schoemaker RC, Pieters MS, Weemaes M, de Rijk R, van der Post J, Cohen AF. Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers. J Clin Psychopharmacol. 2002 Apr;22(2):183-9. PubMed PMID 11910264.
^1: Lowe SL, Yeo KP, Teng L, Soon DK, Pan A, Wise SD, Peck RW. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006 May;31(4):473-84. Epub 2005 Dec 27. PubMed PMID 16378695.
^Ma Z, Zhang G, Jenney C, Krishnamoorthy S, Tao R. (July 2008). "Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats". Eur J Pharmacol.588 (2–3): 198–206. doi:10.1016/j.ejphar.2008.04.004. PMID18499101.
^Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T. (2006). "Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats". Eur J Pharmacol.532 (3): 258–264. doi:10.1016/j.ejphar.2005.12.075. PMID16488409.
^Jacobs G, Kamerling I, de Kam M, et al. (Nov 2008). "Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron". J Psychopharmacol. (Oxford)24 (1): 65–72. doi:10.1177/0269881108094299. PMID18719048.
^Michelson, D; Page, SW, Casey, R, Trucksess, MW, Love, LA, Milstien, S, Wilson, C, Massaquoi, SG, Crofford, LJ, Hallett, M (December 1994). "An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan". The Journal of rheumatology21 (12): 2261–5. PMID7699627.
den Boer JA, Westenberg HG (1990). "Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder". Psychiatry Research31 (3): 267–78. doi:10.1016/0165-1781(90)90096-N. PMID2139731.
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 für Psychiatrie und Nervenkrankheiten224 (2): 175–86. PMID336002.