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{{distinguish|5-hydroxytryptamine}}
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{{Use dmy dates|date=September 2015}}
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{{Distinguish|5-hydroxytryptamine}}
{{chembox
{{About|5-hydroxytryptophan as a biological compound|its role as a medication and supplement|Oxitriptan}}
{{Chembox
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
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| verifiedrevid = 477224677
| verifiedrevid = 477224677
| ImageFile = 5-Hydroxy-L-Tryptophan_(5-HTP).svg
| ImageFile = 5-Hydroxy-L-Tryptophan (5-HTP).svg
| ImageAlt = Skeletal formula
| ImageAlt = Skeletal formula
| ImageFile1 = 5-Hydroxy-L-tryptophan-3D-balls.png
| ImageFile1 = 5-Hydroxy-L-tryptophan-3D-balls.png
| ImageAlt1 = Ball-and-stick model
| ImageAlt1 = Ball-and-stick model
| IUPACName=2-amino-3-(5-hydroxy-1''H''-indol-3-yl)propanoic acid
| IUPACName = 2-amino-3-(5-hydroxy-1''H''-indol-3-yl)propanoic acid
| OtherNames=
| OtherNames = 5-HTP; Oxitriptan
|Section1={{Chembox Identifiers
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4671
| IUPHAR_ligand = 4671
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| StdInChIKey = LDCYZAJDBXYCGN-VIFPVBQESA-N
| StdInChIKey = LDCYZAJDBXYCGN-VIFPVBQESA-N
| CASNo_Ref = {{cascite|changed|CAS}}
| CASNo_Ref = {{cascite|changed|CAS}}
| CASNo=4350-09-8
| CASNo = 56-69-9
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| ChEBI_Ref = {{ebicite|correct|EBI}}
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| ChEBI = 17780
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| SMILES = O=C(O)[C@@H](N)Cc2c1cc(O)ccc1[nH]c2
| SMILES = O=C(O)[C@@H](N)Cc2c1cc(O)ccc1[nH]c2
| MeSHName=5-Hydroxytryptophan
| MeSHName = 5-Hydroxytryptophan
}}
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|Section6={{Chembox Pharmacology
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| ATCCode_suffix = AX01
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'''5-Hydroxytryptophan''' ('''5-HTP'''), also known as '''oxitriptan''', is a [[natural product|naturally occurring]] [[amino acid]] and [[chemical compound|chemical]] [[precursor (chemistry)|precursor]] as well as a [[metabolic intermediate]] in the [[biosynthesis]] of the [[neurotransmitter]] [[serotonin]].
'''5-Hydroxytryptophan''' ('''5-HTP'''), used medically as '''oxitriptan''', is a [[natural product|naturally occurring]] [[amino acid]] and [[chemical compound|chemical]] [[precursor (chemistry)|precursor]] as well as a [[metabolic intermediate]] in the [[biosynthesis]] of the [[neurotransmitter]] [[serotonin]].


5-HTP can be manufactured and used as a [[drug]] and supplement with the {{Abbrlink|INN|International Nonproprietary Name}} ''[[oxitriptan]]''. Brand names include Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. As a drug, it is used in the treatment of [[depression (mood)|depression]] and for certain other indications.
== Uses ==
5-HTP is sold [[over-the-counter|over the counter]] in the [[United States]], [[France]], [[Canada]], [[Singapore]], the [[Netherlands]], and the [[United Kingdom]] as a [[dietary supplement]] for use as an [[antidepressant]], [[appetite suppressant]], and [[sleep aid]]. It is also marketed in many European countries for the indication of [[major depressive disorder|major depression]] under the trade names Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum.<ref name="isbn3-88763-075-0">{{cite book | author = Swiss Pharmaceutical Society | title = Index Nominum 2000: International Drug Directory (Book with CD-ROM) | publisher = Medpharm Scientific Publishers | location = Boca Raton | year = 2000 | isbn = 978-3-88763-075-1 | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA773}}</ref>


⚫
==Production==
A 2002 review concluded that although the data evaluated suggests that 5-HTP is more effective than placebo in the treatment of depression, the evidence was insufficient to be conclusive due to a lack of clinical data meeting the rigorous standards of the day.<ref name="pmid11687048">{{cite journal | vauthors = Shaw K, Turner J, Del Mar C | title = Tryptophan and 5-hydroxytryptophan for depression | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003198 | year = 2002 | volume = 2010 | pmid = 11869656 | doi = 10.1002/14651858.CD003198 | editor1-last = Shaw | editor1-first = Kelly A | url = https://espace.library.uq.edu.au/view/UQ:209937/UQ209937_OA.pdf }}</ref> More and larger studies using current methodologies are needed to determine if 5-HTP is truly effective in treating depression.<ref>{{cite web|url=http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm|title=5-Hydroxytryptophan (5-HTP)|access-date=9 January 2012|publisher=University of Maryland Medical Center| archive-url=https://web.archive.org/web/20170625093048/http://umm.edu/health/medical/altmed/supplement/5hydroxytryptophan-5htp| archive-date=25 June 2017 | url-status=dead}}</ref><ref>{{cite journal | vauthors = Iovieno N, Dalton ED, Fava M, Mischoulon D | title = Second-tier natural antidepressants: review and critique | journal = Journal of Affective Disorders | volume = 130 | issue = 3 | pages = 343–357 | date = May 2011 | pmid = 20579741 | doi = 10.1016/j.jad.2010.06.010 }}</ref> In small, controlled trials 5-HTP has also been reported to augment the antidepressant efficacy of the antidepressant [[clomipramine]].<ref>{{cite journal | vauthors = van Praag HM | title = Serotonin precursors in the treatment of depression | journal = Advances in Biochemical Psychopharmacology | volume = 34 | pages = 259–286 | year = 1982 | pmid = 6753514 }}</ref><ref>{{cite journal | vauthors = van Praag HM, van den Burg W, Bos ER, Dols LC | title = 5-hydroxytryptophan in combination with clomipramine in "therapy-resistant" depressions | journal = Psychopharmacologia | volume = 38 | issue = 3 | pages = 267–269 | year = 1974 | pmid = 4547418 | doi = 10.1007/BF00421379 | s2cid = 11048888 }}</ref><ref>{{cite journal | vauthors = Nardini M, De Stefano R, Iannuccelli M, Borghesi R, Battistini N | title = Treatment of depression with L-5-hydroxytryptophan combined with chlorimipramine, a double-blind study | journal = International Journal of Clinical Pharmacology Research | volume = 3 | issue = 4 | pages = 239–250 | year = 1983 | pmid = 6381336 }}</ref> A 2020 meta-analysis found oral 5-HTP supplementation had a large effect size on depression symptom severity. However, the included studies were considered relatively weak and the methods and treatment duration varied between the seven studies examined.<ref>{{cite journal |last1= Javelle |first1= Florian |last2= Lampit |first2= Amit |last3= Bloch |first3= Wilhelm |last4= Häussermann |first4= Peter |last5= Johnson |first5= Sheri |last6= Zimmer |first6= Philipp |date= 2020 |title= Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis |url= https://academic.oup.com/nutritionreviews/article-abstract/78/1/77/5555860 |journal= Nutrition Reviews |volume= 78 |issue= 1 |pages= 77–88 |doi= 10.1093/nutrit/nuz039|pmid= 31504850 }}</ref>

'''5-HTP use after MDMA'''

[[MDMA]] is an [[empathogen-entactogen|empathogenic-entactogenic]] and [[Serotonin|serotonergic]] [[psychotropic drug]] used primarily for [[recreational drug|recreational]], though sometimes also therapeutic, purposes. Among users of MDMA, the serotonergic effects of the drug are often of particular interest and concern: After consuming MDMA, serotonin concentrations are greatly reduced in the brain. 5-HTP is necessary for serotonin production and its concentrations in the brain also decrease after taking MDMA.

'''Other usage'''

At high doses, or in combination with [[carbidopa]], 5-HTP has been used to treat [[obesity]] (by promoting weight loss).<ref>{{cite journal | vauthors = Halpern B, Oliveira ES, Faria AM, Halpern A, Melo ME, Cercato C, Mancini MC | title = Combinations of drugs in the Treatment of Obesity | journal = Pharmaceuticals | volume = 3 | issue = 8 | pages = 2398–2415 | date = July 2010 | pmid = 27713360 | pmc = 4033931 | doi = 10.3390/ph3082398 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hendricks EJ | title = Off-label drugs for weight management | journal = Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy| volume = 10 | pages = 223–234 | date = 2017 | pmid = 28652791 | pmc = 5473499 | doi = 10.2147/DMSO.S95299 | doi-access = free }}</ref>

In clinical trials of various design, 5-HTP has also been reported to treat [[fibromyalgia]],<ref>{{cite journal | vauthors = Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V | year = 1990 | title = Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome | journal = J Int Med Res. | volume = 18 | issue = 3| pages = 201–209 | pmid = 2193835 | doi = 10.1177/030006059001800304 | s2cid = 27586915 }}</ref> [[myoclonus]],<ref>{{cite journal | pmid = 6969054 | doi=10.1002/ana.410070611 | volume=7 | title=Treatment of myoclonus with L-5-hydroxytryptophan and carbidopa: clinical, electrophysiological, and biochemical observations | year=1980 | journal=Ann Neurol | pages=570–576 | vauthors=Thal LJ, Sharpless NS, Wolfson L, Katzman R | issue=6 | s2cid=11647568 }}</ref> [[migraine]],<ref>{{cite journal | vauthors = Boiardi A, Crenna P, Merati B, Negri S, Tansini E, Bussone G | year = 1981 | title = 5-OH-Tryptophane in migraine: clinical and neurophysiological considerations | journal = J Neurol | volume = 225 | issue = 1| pages = 41–46 | pmid = 6164755 | doi = 10.1007/bf00313460 | s2cid = 2424064 }}</ref> and cerebellar ataxia.<ref>{{cite journal | vauthors = Trouillas P, Brudon F, Adeleine P | date = Nov 1988 | title = Improvement of cerebellar ataxia with levorotatory form of 5-hydroxytryptophan. A double-blind study with quantified data processing | journal = Arch Neurol | volume = 45 | issue = 11| pages = 1217–1222 | pmid = 3190503 | doi = 10.1001/archneur.1988.00520350055016 }}</ref> However, these clinical findings, as for all therapeutic findings with 5-HTP, are preliminary and need confirmation in larger trials.

== Drawbacks ==
5-HTP's short half-life (<2h)<ref name=pmid11910264>{{cite journal | vauthors = Gijsman HJ, van Gerven JM, de Kam ML, Schoemaker RC, Pieters MS, Weemaes M, de Rijk R, van der Post J, Cohen AF | title = Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers | journal = Journal of Clinical Psychopharmacology | volume = 22 | issue = 2 | pages = 183–189 | date = April 2002 | pmid = 11910264 | doi = 10.1097/00004714-200204000-00012 | s2cid = 37414452 }}</ref> may inherently limit its therapeutic potential,<ref name=pmid27692695>{{cite journal | vauthors = Jacobsen JP, Krystal AD, Krishnan KR, Caron MG | title = Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale | journal = Trends in Pharmacological Sciences | volume = 37 | issue = 11 | pages = 933–944 | date = November 2016 | pmid = 27692695 | pmc = 5728156 | doi = 10.1016/j.tips.2016.09.001 }}</ref> as systemic 5-HTP exposure levels will fluctuate substantially even with relatively frequent dosing. Such exposure fluctuations are usually associated with increased adverse event burdens resulting from [[Cmax (pharmacology)|C<sub>max</sub>]] (time to maximal systemic concentration) drug spikes, and decreased clinical efficacy resulting from sub-therapeutic exposure for large parts of the day, when taken as a single dose unit or at intervals significantly larger than C<sub>max</sub>. It has been proposed that 5-HTP dosage forms achieving prolonged delivery would be more effective,<ref name=pmid27692695/> as has been demonstrated many times with other pharmaceuticals with short durations of action.<ref>{{cite journal | vauthors = Thombre AG | title = Assessment of the feasibility of oral controlled release in an exploratory development setting | journal = Drug Discovery Today | volume = 10 | issue = 17 | pages = 1159–1166 | date = September 2005 | pmid = 16182208 | doi = 10.1016/S1359-6446(05)03551-8 }}</ref> For example, controlled release [[oxycodone]] ([[OxyContin]]) or [[morphine]] ([[MS-Contin]]) are intended to, via novel delivery mechanisms, permit pain relief for up to twelve hours with an active ingredient which only provides relief for 3–6 hours. However, the inherent variability amongst different people with respect to drug metabolism makes this task challenging.

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==Side effects==
Potential side effects of 5-HTP include [[heartburn]], stomach pain, [[nausea]], [[vomiting]], [[diarrhea]], [[drowsiness]], [[sexual dysfunction|sexual problems]], vivid dreams or [[nightmares]], and muscle problems.<ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/natural/794.html |title=5-HTP |work=U.S. National Library of Medicine |access-date=7 June 2015}}</ref> Because 5-HTP has not been thoroughly studied in a clinical setting, possible side effects and interactions with other drugs are not well known. According to the US National Library of Medicine, 5-HTP has not been associated with serotonin syndrome or any serious adverse events in humans.<ref name="pubchem.ncbi.nlm.nih.gov">{{Cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/5-Hydroxytryptophan#section=Toxicity |title = 5-Hydroxytryptophan, C11H12N2O3, CID 144 - PubChem}}</ref> Across multiple studies, 5-HTP has also been reported to not cause any noticeable hematological or cardiovascular changes.<ref name="5-Hydroxytryptophan: a review of it">{{cite journal | vauthors = Byerley WF, Judd LL, Reimherr FW, Grosser BI | date = Jun 1987 | title = 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects | journal = J Clin Psychopharmacol | volume = 7 | issue = 3| pages = 127–37 | pmid = 3298325 | doi = 10.1097/00004714-198706000-00002 }}</ref> 5-HTP had also been associated with [[eosinophilia]], but later studies have not found any causal connection.<ref name="ReferenceA">{{cite journal | vauthors = Das YT, Bagchi M, Bagchi D, Preuss HG | year = 2004 | title = Safety of 5-hydroxy-L-tryptophan | journal = Toxicol. Lett. | volume = 150 | issue = 1| pages = 111–22 | pmid = 15068828 | doi = 10.1016/j.toxlet.2003.12.070 }}</ref>

== Interactions ==
When combined with antidepressants of the [[MAOI]] or [[SSRI]] class, very high parenteral doses of 5-HTP can cause acute [[serotonin syndrome]] in rats.<ref>{{cite journal | vauthors = Ma Z, Zhang G, Jenney C, Krishnamoorthy S, Tao R | title = Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats | journal = European Journal of Pharmacology | volume = 588 | issue = 2–3 | pages = 198–206 | date = July 2008 | pmid = 18499101 | pmc = 4242171 | doi = 10.1016/j.ejphar.2008.04.004 }}</ref><ref>{{cite journal | vauthors = Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T | title = Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats | journal = European Journal of Pharmacology | volume = 532 | issue = 3 | pages = 258–64 | date = February 2006 | pmid = 16488409 | doi = 10.1016/j.ejphar.2005.12.075 }}</ref> It is unclear if such findings have clinical relevance, as most drugs will cause serious adverse events or death in rodents at very high doses. In humans 5-HTP has never been clinically associated with serotonin syndrome, although a case report suggests 5-HTP can precipitate mania when added to an MAOI.<ref>{{cite journal | vauthors = Pardo JV | title = Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor | journal = General Hospital Psychiatry | volume = 34 | issue = 1 | pages = 102.e13–4 | date = 2012 | pmid = 21963353 | pmc = 3253963 | doi = 10.1016/j.genhosppsych.2011.08.014 }}</ref>

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]].<ref>{{cite journal | vauthors = Jacobs GE, Kamerling IM, de Kam ML, Derijk RH, van Pelt J, Zitman FG, van Gerven JM | title = Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron | journal = Journal of Psychopharmacology | volume = 24 | issue = 1 | pages = 65–72 | date = January 2010 | pmid = 18719048 | doi = 10.1177/0269881108094299 | s2cid = 23562225 }}</ref> As mentioned below under pharmacology, cases of [[scleroderma]]-like illness have been reported in patients using carbidopa and 5-HTP.<ref>{{cite web|url=http://www.truestarhealth.com/Notes/1339004.html |title=Carbidopa/Levodopa |publisher=Truestarhealth.com |access-date=2014-01-09 |url-status=dead |archive-url=https://web.archive.org/web/20140108185248/http://www.truestarhealth.com/Notes/1339004.html |archive-date=8 January 2014 |df=dmy }}</ref>

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 false positive results in tests looking for [[carcinoid syndrome]].<ref>{{cite journal | vauthors = Joy T, Walsh G, Tokmakejian S, Van Uum SH | title = Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake | journal = Canadian Journal of Gastroenterology | volume = 22 | issue = 1 | pages = 49–53 | date = January 2008 | pmid = 18209781 | pmc = 2659120 | doi = 10.1155/2008/472159 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hallin ML, Mahmoud K, Viswanath A, Gama R | title = 'Sweet Dreams', 'Happy Days' and elevated 24-h urine 5-hydroxyindoleacetic acid excretion | journal = Annals of Clinical Biochemistry | volume = 50 | issue = Pt 1 | pages = 80–2 | date = January 2013 | pmid = 23086978 | doi = 10.1258/acb.2012.012041 | s2cid = 207193834 | doi-access = free }}</ref> Due to the conversion of 5-HTP into serotonin by the liver, there could be a risk of heart valve disease from serotonin's effect on the heart, as based on preclinical findings.<ref name="pmid15781732">{{cite journal | vauthors = Gustafsson BI, Tømmerås K, Nordrum I, Loennechen JP, Brunsvik A, Solligård E, Fossmark R, Bakke I, Syversen U, Waldum H | title = Long-term serotonin administration induces heart valve disease in rats | journal = Circulation | volume = 111 | issue = 12 | pages = 1517–22 | date = March 2005 | pmid = 15781732 | doi = 10.1161/01.CIR.0000159356.42064.48 | s2cid = 3035838 | doi-access = free }}</ref><ref name="pmid12466135">{{cite journal | vauthors = Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B | title = Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells | journal = The American Journal of Pathology | volume = 161 | issue = 6 | pages = 2209–18 | date = December 2002 | pmid = 12466135 | pmc = 1850896 | doi = 10.1016/S0002-9440(10)64497-5 }}</ref> However, 5-HTP has not been associated with cardiac toxicity in humans.<ref name="ReferenceA"/><ref name="5-Hydroxytryptophan: a review of it"/><ref name="pubchem.ncbi.nlm.nih.gov"/><ref>{{cite journal | vauthors = Turner EH, Loftis JM, Blackwell AD | date = Mar 2006 | title = Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan | url = http://www.escholarship.org/uc/item/58h866d5| journal = Pharmacol. Ther. | volume = 109 | issue = 3| pages = 325–38 | pmid = 16023217 | doi = 10.1016/j.pharmthera.2005.06.004 | s2cid = 2563606 }}</ref>

It has been suggested 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 likely caused by a contaminant in certain 5-HTP supplements.<ref>{{cite journal | vauthors = Michelson D, Page SW, Casey R, Trucksess MW, Love LA, Milstien S, Wilson C, Massaquoi SG, Crofford LJ, Hallett M | title = An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan | journal = The Journal of Rheumatology | volume = 21 | issue = 12 | pages = 2261–5 | date = December 1994 | pmid = 7699627 }}</ref>

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== Production ==
5-HTP is produced from the amino acid [[tryptophan]] through the action of the enzyme [[tryptophan hydroxylase]]. Tryptophan hydroxylase is one of the [[biopterin-dependent aromatic amino acid hydroxylases]]. Production of 5-HTP is the rate-limiting step in 5-HT (serotonin) synthesis. 5-HTP is normally rapidly converted to 5-HT by amino acid decarboxylase.<ref>{{cite journal | vauthors = Turner EH, Loftis JM, Blackwell AD | title = Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan | journal = Pharmacology & Therapeutics | volume = 109 | issue = 3 | pages = 325–38 | date = March 2006 | pmid = 16023217 | doi = 10.1016/j.pharmthera.2005.06.004 | s2cid = 2563606 | url = https://escholarship.org/uc/item/58h866d5 }}</ref>
5-HTP is produced from the amino acid [[tryptophan]] through the action of the enzyme [[tryptophan hydroxylase]]. Tryptophan hydroxylase is one of the [[biopterin-dependent aromatic amino acid hydroxylases]]. Production of 5-HTP is the rate-limiting step in 5-HT (serotonin) synthesis. 5-HTP is normally rapidly converted to 5-HT by amino acid decarboxylase.<ref>{{cite journal | vauthors = Turner EH, Loftis JM, Blackwell AD | title = Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan | journal = Pharmacology & Therapeutics | volume = 109 | issue = 3 | pages = 325–38 | date = March 2006 | pmid = 16023217 | doi = 10.1016/j.pharmthera.2005.06.004 | s2cid = 2563606 | url = https://escholarship.org/uc/item/58h866d5 }}</ref>


== Absorption ==
==Metabolism==
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5-HTP is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by the [[enzyme]] [[aromatic-L-amino-acid decarboxylase]] with the help of [[vitamin B6|vitamin B<sub>6</sub>]].<ref>{{cite journal | vauthors = 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 = Japanese Journal of Pharmacology | volume = 32 | issue = 5 | pages = 803–11 | date = October 1982 | pmid = 6983619 | doi = 10.1254/jjp.32.803 | doi-access = free }}</ref> This reaction occurs both in nervous tissue and in the liver.<ref>{{cite journal | vauthors = Bouchard S, Bousquet C, Roberge AG | title = Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat | journal = Journal of Neurochemistry | volume = 37 | issue = 3 | pages = 781–7 | date = September 1981 | pmid = 6974228 | doi = 10.1111/j.1471-4159.1982.tb12555.x | s2cid = 43853143 }}</ref> 5-HTP crosses the [[blood–brain barrier]],<ref>{{cite journal | vauthors = Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H | title = Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat | journal = The European Journal of Neuroscience | volume = 27 | issue = 9 | pages = 2466–72 | date = May 2008 | pmid = 18445233 | doi = 10.1111/j.1460-9568.2008.06201.x | s2cid = 18940166 }}</ref> while 5-HT does not. Excess 5-HTP, especially when administered with vitamin B<sub>6</sub>, is thought to be metabolized and excreted.<ref>{{cite journal | vauthors = Bouchard S, Roberge AG | title = Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat | journal = Canadian Journal of Biochemistry | volume = 57 | issue = 7 | pages = 1014–8 | date = July 1979 | pmid = 39668 | doi = 10.1139/o79-126 }}</ref><ref>{{cite journal | vauthors = 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 Journal of Medical Sciences | volume = 25 | issue = 2–3 | pages = 135–40 | date = September 1976 | pmid = 1088369 }}</ref>
After oral administration, 5-HTP is absorbed by the upper intestine.<ref name=pmid11910264/> The mode of absorption is not known, but presumably involves active transport via amino acid transporters. 5-HTP is adequately absorbed via oral cavity.<ref>{{cite journal | vauthors = Rondanelli M, Opizzi A, Faliva M, Bucci M, Perna S | title = Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration | journal = Eat Weight Disord. | volume = 17 | issue = 1 | date = March 2012 | doi = 10.3275/8165 | pmid = 22142813 | pages = e22-8 | s2cid = 10651414 }}</ref> With a decarboxylase inhibitor, the bioavailability of 5-HTP can be higher than 50%.<ref>{{cite journal | vauthors = Magnussen I, Nielsen-Kudsk F | title = Bioavailability and related pharmacokinetics in man of orally administered L-5-hydroxytryptophan in steady state | journal = Acta Pharmacologica et Toxicologica | volume = 46 | issue = 4 | pages = 257–62 | date = April 1980 | pmid = 6966118 | doi = 10.1111/j.1600-0773.1980.tb02451.x }}</ref>


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[[Image:trp-5ht-pathway.svg|center|600px|Metabolic pathway from tryptophan to serotonin.]]
== Pharmacokinetics ==
5-HTP is rapidly absorbed with a t<sub>max</sub> of {{nowrap|≈1.5{{tsp}}h}}, and rapidly eliminated with a half-life of {{nowrap|≈1.5{{hsp}}{{ndash}}{{hsp}}2{{tsp}}h}}. Co-administration of a decarboxylase inhibitor (''e.g.''{{nbs}}carbidopa, benserazide) doubles the half-life of 5-HTP to {{nowrap|≈{{hsp}}3{{hsp}}{{ndash}}{{hsp}}4{{tsp}}h}},<ref>{{cite journal | vauthors = Magnussen I, Engbaek F | title = The effects of aromatic amino acid decarboxylase inhibitors on plasma concentrations of 5-hydroxytryptophan in man | journal = Acta Pharmacologica et Toxicologica | volume = 43 | issue = 1 | pages = 36–42 | date = July 1978 | pmid = 309271 | doi = 10.1111/j.1600-0773.1978.tb02229.x }}</ref><ref name=pmid11910264/> and enhances exposure several-fold, depending on the dosing regimen.<ref name=pmid11910264/><ref>{{cite journal | vauthors = Westenberg HG, Gerritsen TW, Meijer BA, van Praag HM | title = Kinetics of l-5-hydroxytryptophan in healthy subjects | journal = Psychiatry Research | volume = 7 | issue = 3 | pages = 373–85 | date = December 1982 | pmid = 6187038 | doi = 10.1016/0165-1781(82)90074-9 | s2cid = 45003287 }}</ref>


== Metabolism ==
⚫
5-HTP is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by the [[enzyme]] [[aromatic-L-amino-acid decarboxylase]] with the help of [[vitamin B6|vitamin B<sub>6</sub>]].<ref>{{cite journal | vauthors = 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 = Japanese Journal of Pharmacology | volume = 32 | issue = 5 | pages = 803–11 | date = October 1982 | pmid = 6983619 | doi = 10.1254/jjp.32.803 | doi-access = free }}</ref> This reaction occurs both in nervous tissue and in the liver.<ref>{{cite journal | vauthors = Bouchard S, Bousquet C, Roberge AG | title = Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat | journal = Journal of Neurochemistry | volume = 37 | issue = 3 | pages = 781–7 | date = September 1981 | pmid = 6974228 | doi = 10.1111/j.1471-4159.1982.tb12555.x | s2cid = 43853143 }}</ref> 5-HTP crosses the [[blood–brain barrier]],<ref>{{cite journal | vauthors = Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H | title = Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat | journal = The European Journal of Neuroscience | volume = 27 | issue = 9 | pages = 2466–72 | date = May 2008 | pmid = 18445233 | doi = 10.1111/j.1460-9568.2008.06201.x | s2cid = 18940166 }}</ref> while 5-HT does not. Excess 5-HTP, especially when administered with vitamin B<sub>6</sub>, is thought to be metabolized and excreted.<ref>{{cite journal | vauthors = Bouchard S, Roberge AG | title = Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat | journal = Canadian Journal of Biochemistry | volume = 57 | issue = 7 | pages = 1014–8 | date = July 1979 | pmid = 39668 | doi = 10.1139/o79-126 }}</ref><ref>{{cite journal | vauthors = 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 Journal of Medical Sciences | volume = 25 | issue = 2–3 | pages = 135–40 | date = September 1976 | pmid = 1088369 }}</ref>


{{Enzymatic Reaction
{{Enzymatic Reaction
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}}
}}


⚫
==Dietary sources==
== Pharmacology ==
⚫
{{See also|Tryptophan#Dietary sources}}
The psychoactive action of 5-HTP is derived from its increase in production of serotonin in [[central nervous system]] tissue.<ref>{{cite web|url=http://www.webmd.com/vitamins-supplements/ingredientmono-794-5-HTP.aspx?activeIngredientId=794&activeIngredientName=5-HTP|title=5-HTP: Uses, Side Effects, Interactions and Warnings - WebMD|access-date=2009-10-05| archive-url= https://web.archive.org/web/20091116091605/http://www.webmd.com/vitamins-supplements/ingredientmono-794-5-HTP.aspx?activeIngredientId=794&activeIngredientName=5-HTP| archive-date= 16 November 2009 | url-status= live}}</ref>


⚫
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 all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.<ref>{{cite web|url=http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm|title=5-Hydroxytryptophan|access-date=21 January 2010|publisher=University of Maryland Medical Center| archive-url= https://web.archive.org/web/20100106132618/http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm| archive-date= 6 January 2010 | url-status=dead}}</ref>
⚫
[[Image:trp-5ht-pathway.svg|center|600px|Metabolic pathway from tryptophan to serotonin.]]


==Use as a medication and supplement==
Research shows that co-administration with [[carbidopa]] greatly increases [[blood plasma|plasma]] 5-HTP levels.<ref>{{cite journal | vauthors = 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 | date = September 1981 | pmid = 6175178 | doi = 10.1111/j.1600-0773.1981.tb00890.x }}</ref>
{{Main|Oxitriptan}}
Other studies have indicated the risk of a [[scleroderma]]-like condition resulting from the combination of 5-HTP and carbidopa.<ref>{{cite journal | vauthors = Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, Osterland CK | title = Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa | journal = The New England Journal of Medicine | volume = 303 | issue = 14 | pages = 782–7 | date = October 1980 | pmid = 6997735 | doi = 10.1056/NEJM198010023031403 }}</ref>


5-HTP is used medically and as a supplement under the name ''[[oxitriptan]]'' in the treatment of [[depression (mood)|depression]] and for certain other indications.
== Regulatory status ==
There are currently no approved drug products containing 5-HTP approved by the [[FDA]].<ref>{{Cite web | url=https://www.accessdata.fda.gov/Scripts/cder/ob/index.cfm |title = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations}}</ref> All available 5-HTP products are [[nutraceuticals]] and are as such not regulated or verified for purity, integrity, or clinical efficacy or safety, mandating caution regarding human consumption.<ref>{{Cite web | url=https://medlineplus.gov/druginfo/natural/794.html |title = 5-HTP: MedlinePlus Supplements}}</ref>


It can be potentiated in [[combination drug|combination]] with a [[peripherally selective drug|peripherally selective]] [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AAAD) [[aromatic L-amino acid decarboxylase inhibitor|inhibitor]] such as [[carbidopa]] or [[benserazide]]. These agents increase the strength and duration of oxitriptan. An investigational combination formulation is [[oxitriptan/carbidopa]].
As of 25 August 2020, Hungary added 5-HTP to the controlled psychoactive substances list, prohibiting production, sale, import, storage and use, becoming the first country to do so.<ref>[https://magyarkozlony.hu/hivatalos-lapok/fsmDhb9y0CRKX2SkxRDw5f37b222dc2d1/dokumentumok/bc9ef7aef40a107a518ab17e1ac35adf2735e291/letoltes MAGYARORSZÁG HIVATALOS LAPJA]. Retrieved 2021-04-28.</ref>


==Research==
== 5-HTP slow-release ==
⚫
===Psychedelic effects===
5-HTP's short half-life is impractical for chronic drug therapy. Research conducted at Duke University in mice have demonstrated that 5-HTP when administered as slow-release appears to gain drug properties.<ref name="Jacobsen JP 2016">{{cite journal | vauthors = Jacobsen JP, Rudder ML, Roberts W, Royer EL, Robinson TJ, Oh A, Spasojevic I, Sachs BD, Caron MG | date = Aug 2016 | title = SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept | journal = Neuropsychopharmacology | volume = 41 | issue = 9| pages = 2324–34 | doi = 10.1038/npp.2016.35 | pmid = 26932820 | pmc = 4946063 }}</ref> Slow-release delivery attenuates or abolishes the peaks and valleys in 5-HTP exposure during treatment.<ref>{{cite journal | vauthors = Thombre AG | year = 2005 | title = Assessment of the feasibility of oral controlled release in an exploratory development setting | journal = Drug Discov Today | volume = 10 | issue = 17| pages = 1159–66 | pmid = 16182208 | doi = 10.1016/S1359-6446(05)03551-8 }}</ref> Slow-release delivery of 5-HTP markedly improved the safety profile of 5-HTP and conferred stable plasma exposure of 5-HTP and strong and sustained enhancement of brain serotonin function.<ref name="Jacobsen JP 2016"/> This discovery indicates that 5-HTP slow-release medications represent a new avenue for treatment of brain disorders responsive to serotonergic enhancement.
{{See also|Tryptophan#Psychedelic effects}}


5-HTP robustly produces the [[head-twitch response]] (HTR) in rodents when administered at relatively high doses.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2018" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022">{{cite journal | vauthors = Jaster AM, de la Fuente Revenga M, González-Maeso J | title = Molecular targets of psychedelic-induced plasticity | journal = J Neurochem | volume = 162 | issue = 1 | pages = 80–88 | date = July 2022 | pmid = 34741320 | pmc = 9068831 | doi = 10.1111/jnc.15536 | url = }}</ref><ref name="SchmidBohn2010">{{cite journal | vauthors = Schmid CL, Bohn LM | title = Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a β-arrestin2/Src/Akt signaling complex in vivo | journal = J Neurosci | volume = 30 | issue = 40 | pages = 13513–24 | date = October 2010 | pmid = 20926677 | pmc = 3001293 | doi = 10.1523/JNEUROSCI.1665-10.2010 | url = }}</ref> Similarly, [[intracerebroventricular injection]] of serotonin, but not peripheral administration of serotonin, produces the HTR.<ref name="SchmidBohn2018" /><ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2010" /> The HTR is induced by [[serotonergic psychedelic]]s like [[lysergic acid diethylamide]] (LSD) and [[psilocybin]] and is a behavioral proxy of psychedelic effects.<ref name="CanalMorgan2012">{{cite journal | vauthors = Canal CE, Morgan D | title = Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model | journal = Drug Test Anal | volume = 4 | issue = 7-8 | pages = 556–576 | date = 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 | url = }}</ref><ref name="KozlenkovGonzález-Maeso2013" />
⚫
== Dietary sources ==
⚫
{{See also|Tryptophan#Dietary sources}}
⚫
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 all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.<ref>{{cite web|url=http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm|title=5-Hydroxytryptophan|access-date=21 January 2010|publisher=University of Maryland Medical Center| archive-url= https://web.archive.org/web/20100106132618/http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm| archive-date= 6 January 2010 | url-status=dead}}</ref>


The HTR of 5-HTP is blocked by serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor antagonist|antagonist]]s, which block the [[hallucinogen]]ic effects of serotonergic psychedelics in humans, is prevented by [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AAAD) [[aromatic L-amino acid decarboxylase inhibitor|inhibitor]]s, which block conversion of 5-HTP into serotonin, and is potentiated by [[monoamine oxidase A]] (MAO-A) [[monoamine oxidase inhibitor|inhibitor]]s, which prevent the [[catabolism|degradation]] of serotonin and other [[endogenous]] [[substituted tryptamine|tryptamine]]s.<ref name="SchmidBohn2018">{{cite book | last=Schmid | first=Cullen L. | last2=Bohn | first2=Laura M. | title=5-HT2A Receptors in the Central Nervous System | chapter=βArrestins: Ligand-Directed Regulators of 5-HT2A Receptor Trafficking and Signaling Events | publisher=Springer International Publishing | publication-place=Cham | date=2018 | isbn=978-3-319-70472-2 | doi=10.1007/978-3-319-70474-6_2 | page=31–55}}</ref><ref name="KozlenkovGonzález-Maeso2013" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /><ref name="SchmidBohn2010" /> In addition, the HTR of 5-HTP is abolished by [[indolethylamine N-methyltransferase|indolethylamine ''N''-methyltransferase]] (INMT) [[enzyme inhibitor|inhibitor]]s, which block conversion of serotonin and other endogenous tryptamines into ''N''-[[methyl group|methylated]] tryptamines, such as [[N-Methylserotonin|''N''-methylserotonin]] (NMS; norbufotenin), [[bufotenin]] (5-hydroxy-''N'',''N''-dimethyltryptamine; 5-HO-DMT), and [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT).<ref name="KozlenkovGonzález-Maeso2013">{{cite book | last=Kozlenkov | first=Alexey | last2=González-Maeso | first2=Javier | title=The Neuroscience of Hallucinations | chapter=Animal Models and Hallucinogenic Drugs | publisher=Springer New York | publication-place=New York, NY | date=2013 | isbn=978-1-4614-4120-5 | doi=10.1007/978-1-4614-4121-2_14 | page=253–277}}</ref><ref name="HalberstadtGeyer2018">{{cite journal | vauthors = Halberstadt AL, Geyer MA | title = Effect of Hallucinogens on Unconditioned Behavior | journal = Curr Top Behav Neurosci | volume = 36 | issue = | pages = 159–199 | date = 2018 | pmid = 28224459 | pmc = 5787039 | doi = 10.1007/7854_2016_466 | url = }}</ref><ref name="SchmidBohn2010" /> These ''N''-methylated tryptamines are well-known for their psychedelic effects, whereas serotonin itself, without [[biotransformation]], does not seem to produce psychedelic effects.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2010" /> 5-HTP has not been found to produce psychedelic effects in humans, which has been attributed to the high doses required to produce such effects.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /> The 5-HTP doses that produce the HTR in rodents are orders of magnitude higher than the doses of 5-HTP that have been used safely and therapeutically in humans.<ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /> It remains unknown whether 5-HTP can produce psychedelic effects in humans.<ref name="HanksGonzález-Maeso2013">{{cite journal | vauthors = Hanks JB, González-Maeso J | title = Animal models of serotonergic psychedelics | journal = ACS Chem Neurosci | volume = 4 | issue = 1 | pages = 33–42 | date = January 2013 | pmid = 23336043 | pmc = 3547517 | doi = 10.1021/cn300138m | url = | quote = Following these initial studies, it was shown that a large dose of the serotonin precursor 5-hydroxytryptophan (5-HTP) induces head-twitch behavior in mice.32 However, to our knowledge, equivalent doses of 5-HTP have not been tested in healthy volunteers, and therefore, it remains unknown whether 5-HTP is psychedelic in humans. Subsequently, numerous psychedelic compounds were shown to induce head-twitch behavior.27,33−36}}</ref>
The seeds of the ''[[Griffonia simplicifolia]]'', a climbing shrub native to [[West Africa]] and [[Central Africa]], are used as an herbal supplement for their 5-HTP content.<ref name="ADAM">{{cite web |title=5-Hydroxytryptophan (5-HTP) |publisher=University of Maryland Medical Center |url=http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm |work=[[A.D.A.M., Inc.]]}} Animated Dissection of Anatomy for Medicine, Inc. (A.D.A.M., Inc.) provided health and benefits information and technology to healthcare organizations, employers, consumers, and educational institutions</ref><ref>{{cite journal | vauthors = Emanuele E, Bertona M, Minoretti P, Geroldi D | title = An open-label trial of L-5-hydroxytryptophan in subjects with romantic stress | journal = Neuro Endocrinology Letters | volume = 31 | issue = 5 | pages = 663–6 | year = 2010 | pmid = 21178946 }}</ref><ref name="CID">{{citation | url=https://pubchem.ncbi.nlm.nih.gov/compound/439280 | title=5-hydroxy-L-tryptophan | work=National Center for Biotechnology Information | series=PubChem Compound Database | date=September 2004 }}CID=439280</ref> In one 2010 trial, ''Griffonia simplicifolia'' extract appeared to increase [[Hunger (physiology)|satiety]] in [[overweight]] women.<ref>{{cite journal | vauthors = Rondanelli M, Opizzi A, Faliva M, Bucci M, Perna S | title = Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration | journal = Eating and Weight Disorders | volume = 17 | issue = 1 | pages = e22–8 | date = March 2012 | pmid = 22142813 | doi = 10.3275/8165 | s2cid = 10651414 }}</ref>


The lack of the HTR and psychedelic effects with serotonin itself has been attributed to the fact that these effects appear to be dependent on activation of a population of [[intracellular]] 5-HT<sub>2A</sub> receptors expressed in [[cortex|cortical]] [[neuron]]s in the [[medial prefrontal cortex]] (mPFC) that lack the [[serotonin transporter]] (SERT) and are inaccessible to serotonin.<ref name="Sapienza2023">{{cite journal | last=Sapienza | first=Jacopo | title=The Key Role of Intracellular 5-HT2A Receptors: A Turning Point in Psychedelic Research? | journal=Psychoactives | volume=2 | issue=4 | date=13 October 2023 | issn=2813-1851 | doi=10.3390/psychoactives2040018 | doi-access=free | pages=287–293}}</ref><ref name="VargasDunlapDong2023">{{cite journal | vauthors = Vargas MV, Dunlap LE, Dong C, Carter SJ, Tombari RJ, Jami SA, Cameron LP, Patel SD, Hennessey JJ, Saeger HN, McCorvy JD, Gray JA, Tian L, Olson DE | title = Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors | journal = Science | volume = 379 | issue = 6633 | pages = 700–706 | date = February 2023 | pmid = 36795823 | pmc = 10108900 | doi = 10.1126/science.adf0435 | url = }}</ref> Serotonin itself is too [[hydrophilic]] to enter serotonergic neurons without the SERT, whereas serotonergic psychedelics and serotonin's ''N''-methylated [[metabolite]]s and [[structural analogue|analogue]]s are [[lipophilic]] and readily enter these neurons.<ref name="Sapienza2023" /><ref name="VargasDunlapDong2023" /> These findings may also explain why [[selective serotonin reuptake inhibitor]]s (SSRIs) and related serotonergic agents do not produce psychedelic effects.<ref name="Sapienza2023" />
== See also ==
* [[Cardiac fibrosis]]
* [[Melatonin]]
* [[N-Acetylserotonin|''N''-Acetylserotonin]]
* [[Selective serotonin reuptake inhibitor]]
⚫
* [[Serotonin]]
* [[Tryptophan]]


== References ==
==See also==
* [[α-Methyl-5-hydroxytryptophan]]
{{reflist|30em}}

==References==
{{Reflist}}


{{Antidepressants}}
{{Anxiolytics}}
{{Anorectics}}
{{Hypnotics}}
{{Neurotransmitter metabolism intermediates}}
{{Neurotransmitter metabolism intermediates}}
{{Serotonin receptor modulators}}
{{Serotonergics}}
{{Tryptamines}}
{{Tryptamines}}


{{DEFAULTSORT:Hydroxytryptophan, 5-}}
{{DEFAULTSORT:Hydroxytryptophan, 5-}}

⚫
[[Category:Dietary supplements]]
[[Category:Nootropics]]
[[Category:Tryptamines]]
[[Category:Alpha-Amino acids]]
[[Category:Alpha-Amino acids]]
[[Category:Hydroxyarenes]]
[[Category:Hydroxyarenes]]
[[Category:Monoamine precursors]]
[[Category:Monoamine precursors]]
⚫
[[Category:Serotonin]]
⚫
[[Category:Tryptamines]]

Latest revision as of 05:04, 26 November 2024

Not to be confused with 5-hydroxytryptamine.
This article is about 5-hydroxytryptophan as a biological compound. For its role as a medication and supplement, see Oxitriptan.
5-Hydroxytryptophan
Skeletal formula
Ball-and-stick model
Names
IUPAC name
2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Other names
5-HTP; Oxitriptan
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.022.193 Edit this at Wikidata
KEGG
MeSH 5-Hydroxytryptophan
UNII
  • InChI=1S/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)/t9-/m0/s1 checkY
    Key: LDCYZAJDBXYCGN-VIFPVBQESA-N checkY
  • InChI=1/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)/t9-/m0/s1
    Key: LDCYZAJDBXYCGN-VIFPVBQEBZ
  • O=C(O)[C@@H](N)Cc2c1cc(O)ccc1[nH]c2
Properties
C11H12N2O3
Molar mass 220.228 g·mol−1
Density 1.484 g/mL
Melting point 298 to 300 °C (568 to 572 °F; 571 to 573 K)
Boiling point 520.6 °C (969.1 °F; 793.8 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.

5-HTP can be manufactured and used as a drug and supplement with the INNTooltip International Nonproprietary Name oxitriptan. Brand names include Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. As a drug, it is used in the treatment of depression and for certain other indications.

Production

[edit]

5-HTP is produced from the amino acid tryptophan through the action of the enzyme tryptophan hydroxylase. Tryptophan hydroxylase is one of the biopterin-dependent aromatic amino acid hydroxylases. Production of 5-HTP is the rate-limiting step in 5-HT (serotonin) synthesis. 5-HTP is normally rapidly converted to 5-HT by amino acid decarboxylase.[1]

Metabolism

[edit]

5-HTP is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6.[2] This reaction occurs both in nervous tissue and in the liver.[3] 5-HTP crosses the blood–brain barrier,[4] while 5-HT does not. Excess 5-HTP, especially when administered with vitamin B6, is thought to be metabolized and excreted.[5][6]

Metabolic pathway from tryptophan to serotonin.
Metabolic pathway from tryptophan to serotonin.


5-HTP AAAD Serotonin
 
PLP
 
 


Dietary sources

[edit]
See also: Tryptophan § Dietary sources

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 all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.[7]

Use as a medication and supplement

[edit]
Main article: Oxitriptan

5-HTP is used medically and as a supplement under the name oxitriptan in the treatment of depression and for certain other indications.

It can be potentiated in combination with a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor such as carbidopa or benserazide. These agents increase the strength and duration of oxitriptan. An investigational combination formulation is oxitriptan/carbidopa.

Research

[edit]

Psychedelic effects

[edit]
See also: Tryptophan § Psychedelic effects

5-HTP robustly produces the head-twitch response (HTR) in rodents when administered at relatively high doses.[8][9][10][11] Similarly, intracerebroventricular injection of serotonin, but not peripheral administration of serotonin, produces the HTR.[9][8][11] The HTR is induced by serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin and is a behavioral proxy of psychedelic effects.[12][8]

The HTR of 5-HTP is blocked by serotonin 5-HT2A receptor antagonists, which block the hallucinogenic effects of serotonergic psychedelics in humans, is prevented by aromatic L-amino acid decarboxylase (AAAD) inhibitors, which block conversion of 5-HTP into serotonin, and is potentiated by monoamine oxidase A (MAO-A) inhibitors, which prevent the degradation of serotonin and other endogenous tryptamines.[9][8][10][11] In addition, the HTR of 5-HTP is abolished by indolethylamine N-methyltransferase (INMT) inhibitors, which block conversion of serotonin and other endogenous tryptamines into N-methylated tryptamines, such as N-methylserotonin (NMS; norbufotenin), bufotenin (5-hydroxy-N,N-dimethyltryptamine; 5-HO-DMT), and N,N-dimethyltryptamine (DMT).[8][13][11] These N-methylated tryptamines are well-known for their psychedelic effects, whereas serotonin itself, without biotransformation, does not seem to produce psychedelic effects.[8][11] 5-HTP has not been found to produce psychedelic effects in humans, which has been attributed to the high doses required to produce such effects.[8][10] The 5-HTP doses that produce the HTR in rodents are orders of magnitude higher than the doses of 5-HTP that have been used safely and therapeutically in humans.[10] It remains unknown whether 5-HTP can produce psychedelic effects in humans.[14]

The lack of the HTR and psychedelic effects with serotonin itself has been attributed to the fact that these effects appear to be dependent on activation of a population of intracellular 5-HT2A receptors expressed in cortical neurons in the medial prefrontal cortex (mPFC) that lack the serotonin transporter (SERT) and are inaccessible to serotonin.[15][16] Serotonin itself is too hydrophilic to enter serotonergic neurons without the SERT, whereas serotonergic psychedelics and serotonin's N-methylated metabolites and analogues are lipophilic and readily enter these neurons.[15][16] These findings may also explain why selective serotonin reuptake inhibitors (SSRIs) and related serotonergic agents do not produce psychedelic effects.[15]

See also

[edit]

References

[edit]
  1. ^ Turner EH, Loftis JM, Blackwell AD (March 2006). "Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan". Pharmacology & Therapeutics. 109 (3): 325–38. doi:10.1016/j.pharmthera.2005.06.004. PMID 16023217. S2CID 2563606.
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