5-Hydroxytryptophan

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5-Hydroxytryptophan
Chemical name	5-Hydroxytryptophan 5-HTP (S)-2-Amino-3-(5-hydroxy-1H- indol-3-yl)propanoic acid
Chemical formula	C11H12N2O3
Molecular mass	220.22458 g/mol
CAS number	[56-69-9]
SMILES	Oc1cc2c(C[C@@](N)([H]) C(O)=O)c[nH]c2cc1
Disclaimer and references

5-Hydroxytryptophan or 5-HTP is a naturally-occurring amino acid, a 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.

Contents 1 Pharmacology 2 5-HTP as therapeutic supplement 2.1 Research 2.2 Uses 2.3 Dosage 2.4 Side effects 3 See also 4 References 5 Further reading

[edit] Pharmacology

5-Hydroxytryptophan* is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of Vitamin B6 ^[1]. This reaction occurs both in nervous tissue and in the liver ^[2]. 5-HTP crosses the blood-brain barrier, while 5-HT does not. Excess 5-HTP, especially when administered with Vitamin B6, is hypothesized to be metabolized and excreted before reaching the brain ^[3][4].

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 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 their side effects which include vomiting, and potentially fibrosis of the heart).^[5] Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels.^[6]

However, there are also studies that show 5-HTP as beneficial when taken without a PDI (such as Carbidopa) and refuting its adverse effects on the heart. ^[7]

[edit] 5-HTP as therapeutic supplement

5-HTP, which is found in infinitesimal amounts in certain foods like turkey and cheese, 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 usually sold in gelatin capsules. These capsules typically contain either 50mg or 100mg of 5-HTP per capsule. It is recommended to take it on an empty stomach before falling asleep, or in smaller doses throughout the day.^{[citation needed]}

[edit] Research

It has been alleged that 5-HTP can be used to treat mental disorders such as 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.^[8] Some caution and diligence should be exhibited regarding 5-HTP barring further study and review.

Reductions in serotonergic tone are partially responsible for cognitive deficits (memory loss) resulting from tetrahydrocannibinol (THC, the active component in marijuana). 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. When given to rats, 5-HTP can significantly attenuate THC-induced memory impairment. Similar benefits have been seen in those with cognitive deficits resulting from psychostimulant use.^[9]

[edit] Uses

In recent years 5-HTP has been sold by health food companies as an alternative treatment for 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.^{[citation needed]}

5-HTP is also used as a supplement by users of MDMA (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. A temporary decline in serotonin levels is only one of several factors in post-MDMA use cognitive disruptions; neuroadaptive changes in receptor density likely play a larger long-term role.[3] 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. Anecdotal reports seem to indicate this is largely placebo with some users reporting a moderate muting of the MDMA effect.^[10]

[edit] Dosage

Though there is no official dosage, most supplement providers recommend 50 mg or 100 mg 5-HTP, one to three times per day. Contrary to the recommendations of supplement providers, 5-HTP should not be taken concomitant with Vitamin B6, as the combination can lead to toxic accumulation of 5-HT (serotonin) in the blood^[11]. 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, e.g. ^[12] Although many studies do not report a dosing schedule, the majority of those that do have reported using two to four doses split throughout the day.^[13]

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.^[13] In dogs, doses of 23.6 mg/kg were found to cause toxic reactions, although the dose response curve for dogs does not necessarily scale to humans.^[14] Some users report high doses (300 mg and over) can produce nausea and vomiting.^[15]

[edit] Side effects

Promoters of 5-HTP claim that it causes fewer side effects than traditional antidepressants. Side effects of 5-HTP may include nausea, constipation, gas, drowsiness, or a decreased sex drive. It can also have adverse interactions with other natural and traditional drugs.^[16]

[edit] See also

• Serotonin
• Tryptophan
• Vitamin B6
• Pyridoxal Phosphate (PLP) - Bioactive form of vitamin B6

[edit] References

1. ^ Rahman MK et al. Effect of pyridoxal phosphate...[PMID 6983619]
2. ^ 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
3. ^ Bouchard S, Roberge AG. Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat. Can J Biochem. 1979 Jul;57(7):1014-8. [PMID 39668]
4. ^ Hiroshima J Med Sci 1976 Sep;25(2-3):135-40 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. Amamoto T, Sarai K [PMID 1088369]
5. ^ Usenet post by Steven B. Harris: "5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award"
6. ^ Magnussen I. et al. (1981): "Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man.", Acta Pharmacol. Toxicol. (Copenh), Vol. 49(3), 184-9 PMID 6175178
7. ^ http://www.mwilliamson.com/5htps.htm
8. ^ Meyers S 2000 Feb "Use of neurotransmitter precursors for treatment of depression". Altern Med Rev 5(1), 64-71, PMID 10696120
9. ^ Eur J Pharmacol. 2002 Jun 12;445(3):221-9. 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. PMID 12079687
10. ^ MDMA and 5-HTP information and advice
11. ^ Usenet post by Steven B. Harris: "5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award"
12. ^ Magnussen I, Van Woert MH. Eur J Clin Pharmacol 1982;23(1):81-6. Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors. PMID 6182005
13. ^ ^{a b} PMID 16023217
14. ^ PMID 10863592
15. ^ [1]
16. ^ [2]

[edit] Further reading

• U. S. Food and Drug Administration February 2001 "Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan"
• den Boer JA, Westenberg HG 1990 Mar "Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder." Psychiatry Res 31(3), 267-78
• Angst J, Woggon B, Schoepf J 1977 Oct "The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study." Arch Psychiatr Nervenkr. 224(2), 175-86
• Whole Health MD: 5-HTP
• Psychology Today article
• Turner EH, Loftis JM, Blackwell AD, "Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan", Pharmocological Theraputics, 2005 Jul. 13. PMID: 16023217
• Erowid L-tryptophan and 5-HTP Information Vault
• 5-Hydroxytryptophan (5-HTP) Supplement Information (University of Maryland Medical Center)