5-Hydroxytryptophan: Difference between revisions

Line 2:

'''5-Hydroxytryptophan''', also known as '''5-HTP''' and '''oxitriptan''', is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitters [[serotonin]] and [[melatonin]] from [[tryptophan]]. It is available over the counter in the United States, United Kingdom, and Canada as a dietary supplement and often used as an [[antidepressant]], sleep aid, and appetite suppressant. In some European countries, it is marketed as a prescription drug for the treatment of major depression.<ref>https://books.google.com/books?id=5GpcTQD_L2oC&lpg=PA1528&pg=PA773&hl=en#v=onepage&q&f=false | Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0.</ref>

5-HTP is also popularly used by users of [[MDMA]] and other serotonin-releasing agents to reduce the negative [[MDMA#After_effects|after effects]] that begin during the drug's [[duration|come down]] period, including [[anxiety]], [[depression]], and [[cognitive fatigue]].<ref>http://www.sciencedirect.com/science/article/pii/S0306452207006732 | Wang, X.; Baumann, M. H.; Dersch, C. M.; Rothman, R. B. (2007-08-10). "Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan". Neuroscience. 148 (1): 212–220. doi:10.1016/j.neuroscience.2007.05.024. PMID 17629409.</ref> Since 5-HTP is a precursor for the neurotransmitter [[serotonin]] and MDMA depletes both serotonin levels in the brain as well as inhibit the enzyme needed to produce it (tryptophan hydroxylase) for a short term after.<ref>Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulhydrl sites | http://www.maps.org/images/pdf/1989_stone_1.pdf</ref>, it is believed that taking 5-HTP after coming down will speed the production of serotonin and decrease the time needed to recover (though there are many popular misconceptions and controversies about just how effective it is for this purpose).

5-HTP is also popularly used by users of [[MDMA]] and other serotonin-releasing agents to reduce the negative [[MDMA#After_effects|after effects]] that begin during the drug's [[duration|come down]] period, including [[anxiety]], [[depression]], and [[cognitive fatigue]].<ref>http://www.sciencedirect.com/science/article/pii/S0306452207006732 | Wang, X.; Baumann, M. H.; Dersch, C. M.; Rothman, R. B. (2007-08-10). "Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan". Neuroscience. 148 (1): 212–220. doi:10.1016/j.neuroscience.2007.05.024. PMID 17629409.</ref> Since 5-HTP is a precursor for the neurotransmitter [[serotonin]] and MDMA depletes both serotonin levels in the brain as well as inhibit the enzyme needed to produce it (tryptophan hydroxylase) for a short term after.<ref>Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulhydrl sites | http://www.maps.org/images/pdf/1989_stone_1.pdf</ref>, it is believed that taking 5-HTP after coming down will speed the production of serotonin and decrease the time needed to recover (though there are many popular misconceptions and controversies about just how effective it is for this purpose).{{Citation needed}}

5-HTP should not be taken until 12 hours after one's last dose of MDMA because combining the two drugs ~~-- both of which~~ increase serotonin -- ~~could result~~ in a potentially life-threatening condition called [[serotonin syndrome]].

5-HTP should not be taken until 12 hours after one's last dose of MDMA because combining the two drugs could synergistically increase brain's serotonin levels to dangerous degrees -- resulting in a potentially life-threatening condition called [[serotonin syndrome]].

==Chemistry==

==Pharmacology==

The psychoactive action of 5-HTP is derived from its increase in production of serotonin in central nervous system tissue. 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.<ref>https://www.ncbi.nlm.nih.gov/pubmed/6983619 | Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats.</ref> This reaction occurs both in nervous tissue and in the liver.<ref>https://www.ncbi.nlm.nih.gov/pubmed/6974228 | Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat.</ref> 5-HTP crosses the blood–brain barrier,<ref>https://www.ncbi.nlm.nih.gov/pubmed/18445233 | Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat.</ref> while 5-HT does not.

5-HTP is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by [[aromatic-L-amino-acid decarboxylase]] with the help of [[vitamin B6|vitamin B<sub>6</sub>]].<ref>{{Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats | doi=10.1254/jjp.32.803}}</ref> This reaction occurs both in nervous tissue and in the liver.<ref>Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat | doi = 10.1111/j.1471-4159.1982.tb12555.x</ref> 5-HTP crosses the [[blood–brain barrier]],<ref>Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat | doi=10.1111/j.1460-9568.2008.06201.x</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>Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat | doi=10.1139/o79-126}}</ref><ref>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 | |pmid=1088369 </ref>

==Subjective effects==

@@ Line 2: / Line 2: @@
 '''5-Hydroxytryptophan''', also known as '''5-HTP''' and '''oxitriptan''', is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitters [[serotonin]] and [[melatonin]] from [[tryptophan]]. It is available over the counter in the United States, United Kingdom, and Canada as a dietary supplement and often used as an [[antidepressant]], sleep aid, and appetite suppressant. In some European countries, it is marketed as a prescription drug for the treatment of major depression.<ref>https://books.google.com/books?id=5GpcTQD_L2oC&lpg=PA1528&pg=PA773&hl=en#v=onepage&q&f=false | Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0.</ref>
--HTP is also popularly used by users of [[MDMA]] and other serotonin-releasing agents to reduce the negative [[MDMA#After_effects|after effects]] that begin during the drug's [[duration|come down]] period, including [[anxiety]], [[depression]], and [[cognitive fatigue]].<ref>http://www.sciencedirect.com/science/article/pii/S0306452207006732 | Wang, X.; Baumann, M. H.; Dersch, C. M.; Rothman, R. B. (2007-08-10). "Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan". Neuroscience. 148 (1): 212–220. doi:10.1016/j.neuroscience.2007.05.024. PMID 17629409.</ref> Since 5-HTP is a precursor for the neurotransmitter [[serotonin]] and MDMA depletes both serotonin levels in the brain as well as inhibit the enzyme needed to produce it (tryptophan hydroxylase) for a short term after.<ref>Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulhydrl sites | http://www.maps.org/images/pdf/1989_stone_1.pdf</ref>, it is believed that taking 5-HTP after coming down will speed the production of serotonin and decrease the time needed to recover (though there are many popular misconceptions and controversies about just how effective it is for this purpose).
+-HTP is also popularly used by users of [[MDMA]] and other serotonin-releasing agents to reduce the negative [[MDMA#After_effects|after effects]] that begin during the drug's [[duration|come down]] period, including [[anxiety]], [[depression]], and [[cognitive fatigue]].<ref>http://www.sciencedirect.com/science/article/pii/S0306452207006732 | Wang, X.; Baumann, M. H.; Dersch, C. M.; Rothman, R. B. (2007-08-10). "Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of l-5-hydroxytryptophan". Neuroscience. 148 (1): 212–220. doi:10.1016/j.neuroscience.2007.05.024. PMID 17629409.</ref> Since 5-HTP is a precursor for the neurotransmitter [[serotonin]] and MDMA depletes both serotonin levels in the brain as well as inhibit the enzyme needed to produce it (tryptophan hydroxylase) for a short term after.<ref>Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulhydrl sites | http://www.maps.org/images/pdf/1989_stone_1.pdf</ref>, it is believed that taking 5-HTP after coming down will speed the production of serotonin and decrease the time needed to recover (though there are many popular misconceptions and controversies about just how effective it is for this purpose).{{Citation needed}}
--HTP should not be taken until 12 hours after one's last dose of MDMA because combining the two drugs -- both of which increase serotonin -- could result in a potentially life-threatening condition called [[serotonin syndrome]].
+-HTP should not be taken until 12 hours after one's last dose of MDMA because combining the two drugs could synergistically increase brain's serotonin levels to dangerous degrees -- resulting in a potentially life-threatening condition called [[serotonin syndrome]].
 ==Chemistry==
 {{chemistry}}
 ==Pharmacology==
 The psychoactive action of 5-HTP is derived from its increase in production of serotonin in central nervous system tissue. 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.<ref>https://www.ncbi.nlm.nih.gov/pubmed/6983619 | Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats.</ref> This reaction occurs both in nervous tissue and in the liver.<ref>https://www.ncbi.nlm.nih.gov/pubmed/6974228 | Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat.</ref> 5-HTP crosses the blood–brain barrier,<ref>https://www.ncbi.nlm.nih.gov/pubmed/18445233 | Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat.</ref> while 5-HT does not.
+-HTP is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by [[aromatic-L-amino-acid decarboxylase]] with the help of [[vitamin B6|vitamin B<sub>6</sub>]].<ref>{{Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats | doi=10.1254/jjp.32.803}}</ref>  This reaction occurs both in nervous tissue and in the liver.<ref>Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat | doi = 10.1111/j.1471-4159.1982.tb12555.x</ref>  5-HTP crosses the [[blood–brain barrier]],<ref>Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat | doi=10.1111/j.1460-9568.2008.06201.x</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>Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat | doi=10.1139/o79-126}}</ref><ref>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 | |pmid=1088369 </ref>
 ==Subjective effects==
 {{EffectStub}}