View source for 5-Hydroxytryptophan

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'''5-Hydroxytryptophan''' or '''5-HTP''' is a naturally-occurring [[amino acid]], a [[Protein precursor|precursor]] to the [[neurotransmitter]] [[serotonin]] and an intermediate in [[tryptophan]] [[metabolism]]. It is marketed in the [[United States]] and other countries as a dietary supplement for use as an [[antidepressant]], [[appetite suppressant]], and [[sleep aid]].

==Metabolism==

5-Hydroxytryptophan is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by the [[enzyme]] [[aromatic-L-amino-acid decarboxylase]] with the help of [[Vitamin B6]].<ref>{{cite journal |author=Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M |title=Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats |journal=Jpn. J. Pharmacol. |volume=32 |issue=5 |pages=803-11 |year=1982 |pmid=6983619 |doi=}}</ref>  

This reaction occurs both in nervous tissue and in the liver.<ref>Bouchard S, Bousquet C, Roberge AG. 	Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat.  J Neurochem. 1981 Sep;37(3):781-7. PMID 6974228</ref>  5-HTP crosses the [[blood-brain barrier]], while 5-HT does not.  Excess 5-HTP, especially when administered with [[Vitamin B6]], is thought to be metabolized and excreted before reaching the brain.<ref>{{cite journal |author=Bouchard S, Roberge AG |title=Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat |journal=Can. J. Biochem. |volume=57 |issue=7 |pages=1014-8 |year=1979 |pmid=39668 |doi=}}</ref><ref>{{cite journal |author=Amamoto T, Sarai K |title=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 |journal=Hiroshima J. Med. Sci. |volume=25 |issue=2-3 |pages=135-40 |year=1976 |pmid=1088369 |doi=}}</ref>

==Pharmacology==
The psychoactive action of 5-HTP is thought to derive from its effect on serotonin synthesis in [[central nervous system]] tissue. It is believed that an artificially high supply of 5-HTP causes the brain's serotonin-producing neurons to increase production. Increased serotonin production then leads to increased serotonin release.

Some doctors suggest that 5-HTP be administered with a peripheral decarboxylase inhibitor (PDI) such as [[carbidopa]] (and without [[Vitamin B6]], see above) in order to prevent 5-HTP's metabolism in the liver, which can lead to elevated levels of serotonin in the bloodstream (and side effects which include [[vomiting]], and potentially [[fibrosis]] of the [[heart]]).<ref>Usenet post by Steven B. Harris: [http://yarchive.net/med/5-htp.html "5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award"]</ref> Research shows that co-administration with carbidopa greatly increases [[blood plasma|plasma]] 5-HTP levels.<ref>{{cite journal |author=Magnussen I, Jensen TS, Rand JH, Van Woert MH |title=Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man |journal=Acta pharmacologica et toxicologica |volume=49 |issue=3 |pages=184-9 |year=1981 |pmid=6175178 |doi=}}</ref>  However, several studies have reported that 5-HTP is effective even without a PDI.<!-- Removed: "and refuting its adverse effects on the heart". The studies did not address that issue. --><ref>{{cite journal |author=Birdsall TC |title=5-Hydroxytryptophan: a clinically-effective serotonin precursor |journal=Alternative medicine review : a journal of clinical therapeutic |volume=3 |issue=4 |pages=271-80 |year=1998 |pmid=9727088 |doi=}}</ref><ref>http://www.mwilliamson.com/5htps.htm</ref>
Other studies have indicated the risk of a [[scleroderma]]-like condition resulting from the combination of 5-HTP and carbidopa.<ref>{{cite journal |author=Sternberg EM, Van Woert MH, Young SN, ''et al'' |title=Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa |journal=N. Engl. J. Med. |volume=303 |issue=14 |pages=782-7 |year=1980 |pmid=6997735 |doi=}}</ref>

==5-HTP as therapeutic supplement== 
5-HTP, which is found in minute amounts in certain foods like [[turkey]] and [[cheese]]{{Fact|date=October 2007}}, is often sold as an over-the-counter therapeutic supplement. In this case, it is usually sourced from the seeds of ''[[Griffonia simplicifolia]]''. Production of 5-HTP as a supplement increased when a similar serotonin-altering supplement, [[L-tryptophan]], was temporarily barred from sale in the United States by the [[FDA]]. 5-HTP in supplement form is typically sold in 50 mg or 100 mg [[gelatin]] capsules. 

===Risks and Side Effects===

5-HTP raises blood serotonin levels, and because of the risks associated with elevated levels it should only be taken under the advice of a medical professional (See [[Serotonin#Chronic_diseases_resulting_from_serotonin_5-HT2B_overstimulation|Chronic diseases resulting from serotonin 5-HT2B overstimulation]]). For instance, elevated blood serotonin levels are associated with cardiac valve failure and acute or chronic pulmonary hypertension. 

Comprehensive clinical data on other side-effects of 5-HTP are not available. Nevertheless, some product marketers claim that it causes fewer side effects than traditional antidepressants. The basis for these claims are anecdotal and have not been verified scientifically. Side effects of 5-HTP may include nausea, constipation, gas, drowsiness, decreased sex drive, anxiety, numbness, paresthesia, breathing problems, palpitations, chest pain, hallucinations and insomnia. 5-HTP can also have adverse interactions with other natural and traditional drugs.
[http://www.wholehealthmd.com/refshelf/substances_view/1,1525,747,00.html]

===Research===

[[Image:trp-5ht-pathway.png|thumb|600px|Metabolic pathway from tryptophan to serotonin.]]

It has been alleged that 5-HTP can be used to treat mental disorders such as [[clinical depression|depression]]. Unfortunately, the studies to date are incomplete. Reviews of these studies do indicate that potential exists for 5-HTP in the treatment of depression, but further trials are stressed as necessary before arriving at any firm conclusion.<ref name="meyers2000">''Altern Med Rev.''  2000 Feb; 5(1), 64-71 [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=10696120 ''Use of neurotransmitter precursors for treatment of depression.''], Meyers S.</ref> 

Similar deficits have been observed in long term/high dose psychostimulant users. Such deficits are especially apparent  in those who have used amphetamine and methamphetamine. Amphetamines, and to a lesser extent cocaine, can damage serotonergic neurons in the CNS. Similar benefits have been seen in those with cognitive deficits resulting from psychostimulant use.<ref>''Eur J Pharmacol.'' 2002 Jun 12;445(3):221-9. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=12079687 ''Involvement of 5-hydroxytryptamine neuronal system in Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory.''], Egashira N, Mishima K, Katsurabayashi S, Yoshitake T, Matsumoto Y, Ishida J, Yamaguchi M, Iwasaki K, Fujiwara M.</ref>

Current research shows promise in using 5-HTP for treating children with [[night terror]]s. After six months of use 83.9% of the children treated with 5-HTP were free from their persistent nightmares. <ref>''Eur J Pediatr.'' 2004 Jul;163(7):402-7. Epub 2004 May 14. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=15146330 ''L -5-Hydroxytryptophan treatment of sleep terrors in children''], Bruni O, Ferri R, Miano S, Verrillo E.</ref> 

Some persons with [[fibromyalgia]] find that 5-HTP improves their symptoms.<ref>''J Int Med Res.'' 1992 Apr;20(2):182-9 [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=1521674 ''Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study.''], Sarzi Puttini P, Caruso I.</ref> Fibromyalgia sufferers report improvement in sleep, depression, pain and all major complaints related to fibromyalgia.<ref>''J Int Med Res.'' 1990 May-Jun;18(3):201-9. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=2193835 ''Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.''], Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V.</ref> Studies are continuing to refine dosage and continued use.

===Uses===
In recent years 5-HTP has been sold by [[health food]] companies as an alternative treatment for [[clinical depression|depression]] and [[mood disorders]]. Its role as an intermediary in the [[biosynthesis]] of serotonin indicates that this chemical may indeed be effective in treating these and other serotonin-related disorders, but there is some debate on the conclusions of the clinical trials which have been carried out using the drug.{{Fact|date=February 2007}} It is also used as a prophylactic against [[Rebound headache|chronic daily headache]]. <ref>{{cite journal |author=De Benedittis G, Massei R |title=Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. |journal=Journal of Neurosurgical Sciences |volume=29 |issue=3 |pages=239−48 |year=1985 |pmid=3913752}}</ref> 5-HTP may also be useful in treatment for migraines, since studies have shown that migraines occur when serotonin levels are low.  

5-HTP is also used as a supplement by users of [[MDMA]] (commonly known as ecstasy) to help replenish depleted serotonin, in an attempt to alleviate to a degree the depression and overall mental unsettlement that sometimes occurs in the days following MDMA usage. 5-HTP is less commonly used immediately before the use of MDMA as a means to both further reduce the negative psychological effects of depleted serotonin, and as an attempt to boost the effects of MDMA. Some users report a moderate muting of the MDMA effect.<ref>[http://www.erowid.org/ask/ask.cgi?A=Show&QID=1750 MDMA and 5-HTP information and advice]</ref>

===Dosage===
Though there is no official dosage, most supplement providers recommend 50 mg or 100 mg 5-HTP, one to three times per day. Most clinical studies have tested doses of 200-300 mg/day, although one study tested doses as large as 3250 mg/day.  In many clinical studies 5-HTP is administered with [[carbidopa]], which substantially changes 5-HTP's pharmacology. <ref>{{cite journal |author=Magnussen I, Van Woert MH |title=Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors |journal=Eur. J. Clin. Pharmacol. |volume=23 |issue=1 |pages=81-6 |year=1982 |pmid=6182005 |doi=}}</ref>
Although many studies do not report a dosing schedule, the majority of those that do have reported using two to four doses spaced throughout the day. The most effective timing would be before sleep, and on an empty stomach.  Consumption with other proteins or amino acids will decrease absorption in the digestive tract.   <ref name="pubmed: turner et al">{{cite journal |author=Turner EH, Loftis JM, Blackwell AD |title=Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan |journal=Pharmacol. Ther. |volume=109 |issue=3 |pages=325-38 |year=2006 |pmid=16023217 |doi=10.1016/j.pharmthera.2005.06.004}}</ref>

In theory, an overdose of 5-HTP could cause [[serotonin syndrome]]. However, serotonin syndrome was not observed in several studies that augmented traditional antidepressant therapy with 5-HTP, even though the combination therapy was expected to increase the risk of serotonin syndrome above 5-HTP alone.<ref name="pubmed: turner et al"/>  In dogs, doses of 23.6 mg/kg were found to cause toxic reactions, although the dose response curve for any animal with any drug will probably not scale to humans.<ref>{{cite journal |author=Gwaltney-Brant SM, Albretsen JC, Khan SA |title=5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999) |journal=J. Am. Vet. Med. Assoc. |volume=216 |issue=12 |pages=1937-40 |year=2000 |pmid=10863592 |doi=}}</ref> Some users report high doses (300 mg and over) can produce nausea and vomiting.<ref>{{cite web |url=http://www.erowid.org/experiences/exp.cgi?S1=138 |title=Erowid Experience Vaults: Search Results |accessdate=2007-06-09 |format= |work=}}</ref> High doses may be damaging to the liver, due to the fact that the level of each amino acid in the blood must be tightly regulated by removal of any excess.

==See also==
*[[Serotonin]]
*[[Tryptophan]]
*[[Vitamin B6]]
*[[Pyridoxal-phosphate|Pyridoxal Phosphate (PLP)]] - Bioactive form of vitamin B6

==References==
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==Further reading==
*[http://vm.cfsan.fda.gov/~dms/ds-tryp1.html Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan] at [[Food and Drug Administration]], February 2001

* {{cite journal |author=den Boer JA, Westenberg HG |title=Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder |journal=Psychiatry research |volume=31 |issue=3 |pages=267-78 |year=1990 |pmid=2139731 |doi=}}

* {{cite journal |author=Angst J, Woggon B, Schoepf J |title=The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study |journal=Archiv für Psychiatrie und Nervenkrankheiten |volume=224 |issue=2 |pages=175-86 |year=1977 |pmid=336002 |doi=}}

*[http://cms.psychologytoday.com/articles/pto-19981101-000022.html article] at [[Psychology Today]]

* {{cite journal |author=Turner EH, Loftis JM, Blackwell AD |title=Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan |journal=Pharmacol. Ther. |volume=109 |issue=3 |pages=325-38 |year=2006 |pmid=16023217 |doi=10.1016/j.pharmthera.2005.06.004}}

*[http://www.erowid.org/smarts/tryptophan/tryptophan.shtml Erowid L-tryptophan and 5-HTP Information Vault] at [[Erowid]]

*[http://www.umm.edu/altmed/ConsSupplements/5Hydroxytryptophan5HTPcs.html 5-Hydroxytryptophan (5-HTP) Supplement Information] at [[University of Maryland, Baltimore|University of Maryland]] Medical Center

*[http://www.dancesafe.org/slideshow/ MDMA slideshow] at [[DanceSafe]]

{{DEFAULTSORT:Hydroxytryptophan, 5-}}
[[Category:Neurotransmitters]]
[[Category:Dietary supplements]]
[[Category:Nootropics]]
[[Category:Tryptamines]]

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