Editing Tryptophan (section)

=== Psychedelic effects ===
{{See also|5-Hydroxytryptophan#Psychedelic effects}}

Tryptophan produces the [[head-twitch response]] (HTR) in rodents when administered at sufficiently high doses.<ref name="HalberstadtGeyer2018">{{cite book | vauthors = Halberstadt AL, Geyer MA | title = Behavioral Neurobiology of Psychedelic Drugs | chapter = Effect of Hallucinogens on Unconditioned Behavior | series = Current Topics in Behavioral Neurosciences | volume = 36 | issue = | pages = 159–199 | date = 2018 | pmid = 28224459 | pmc = 5787039 | doi = 10.1007/7854_2016_466 | isbn = 978-3-662-55878-2 | chapter-url = }}</ref> 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">{{cite book | last1=Kozlenkov | first1=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 | pages=253–277}}</ref> Tryptophan is converted into the [[trace amine]] [[tryptamine]] and tryptamine is ''N''-[[methyl group|methylated]] by [[indolethylamine N-methyltransferase|indolethylamine ''N''-methyltransferase]] (INMT) into [[N-methyltryptamine|''N''-methyltryptamine]] (NMT) and [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (''N'',''N''-DMT), which are known serotonergic psychedelics.<ref name="HalberstadtGeyer2018" /><ref name="CarbonaroGatch2016">{{cite journal | vauthors = Carbonaro TM, Gatch MB | title = Neuropharmacology of N,N-dimethyltryptamine | journal = Brain Res Bull | volume = 126 | issue = Pt 1 | pages = 74–88 | date = September 2016 | pmid = 27126737 | pmc = 5048497 | doi = 10.1016/j.brainresbull.2016.04.016 | url = | quote = Endogenous DMT is synthesized from the essential amino acid tryptophan, which is decarboxylated to tryptamine. Tryptamine is then transmethylated by the enzyme indolethylamine-N-methyltransferase (INMT) (using S-adenosyl methionine as a substrate), which catalyzes the addition of methyl groups resulting in the production of N-methyltryptamine (NMT) and DMT. NMT can also act as a substrate for INMT-dependent DMT biosynthesis (Barker et al., 1981).}}</ref><ref name="Barker2018">{{cite journal | vauthors = Barker SA | title = N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function | journal = Front Neurosci | volume = 12 | issue = | pages = 536 | date = 2018 | pmid = 30127713 | pmc = 6088236 | doi = 10.3389/fnins.2018.00536 | doi-access = free | url = | quote = After the discovery of an indole-N-methyl transferase (INMT; Axelrod, 1961) in rat brain, researchers were soon examining whether the conversion of tryptophan (2, Figure 2) to tryptamine (TA; 3, Figure 2) could be converted to DMT in the brain and other tissues from several mammalian species. Numerous studies subsequently demonstrated the biosynthesis of DMT in mammalian tissue preparations in vitro and in vivo (Saavedra and Axelrod, 1972; Saavedra et al., 1973). In 1972, Juan Saavedra and Julius Axelrod reported that intracisternally administered TA was converted to N-methyltryptamine (NMT; 4, Figure 2) and DMT in the rat, the first demonstration of DMT’s formation by brain tissue in vivo.}}</ref><ref name="CameronOlson2018">{{cite journal | vauthors = Cameron LP, Olson DE | title = Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT) | journal = ACS Chem Neurosci | volume = 9 | issue = 10 | pages = 2344–2357 | date = October 2018 | pmid = 30036036 | doi = 10.1021/acschemneuro.8b00101 | url = https://shaunlacob.com/wp-content/uploads/2020/12/Dark-Classics-DMT.pdf | quote=Like serotonin and melatonin, DMT is a product of tryptophan metabolism.25 Following tryptophan decarboxylation, tryptamine is methylated by an N-methyltransferase (i.e., INMT) with S-adenosylmethionine serving as the methyl donor. A second enzymatic methylation produces DMT (Figure 3A).26 [...] The enzyme indolethylamine N-methyltransferase (INMT) catalyzes the methylation of a variety of biogenic amines, and is responsible for converting tryptamine into DMT in mammals.140}}</ref><ref name="ColosimoBorsellinoKrider2024">{{cite journal | last1=Colosimo | first1=Frankie A. | last2=Borsellino | first2=Philip | last3=Krider | first3=Reese I. | last4=Marquez | first4=Raul E. | last5=Vida | first5=Thomas A. | title=The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness | journal=Psychoactives | publisher=MDPI AG | volume=3 | issue=1 | date=26 February 2024 | issn=2813-1851 | doi=10.3390/psychoactives3010007 | doi-access=free | pages=93–122 | quote=The metabolism of DMT within the body begins with its synthesis. Endogenous DMT is made from tryptophan after decarboxylation transforms it into tryptamine [22,25]. Tryptamine then undergoes transmethylation mediated by indolethylamine-N-methyltransferase (INMT) with S-adenosyl methionine (SAM) as a substrate, morphing into N-methyltryptamine (NMT) and eventually producing N,N-DMT [26]. Intriguingly, INMT is distributed widely across the body, predominantly in the lungs, thyroid, and adrenal glands, with a dense presence in the anterior horn of the spinal cord. Within the cerebral domain, regions such as the uncus, medulla, amygdala, frontal cortex, fronto-parietal lobe, and temporal lobe exhibit INMT activity, primarily localized in the soma [26]. INMT transcripts are found in specific brain regions, including the cerebral cortex, pineal gland, and choroid plexus, in both rats and humans. Although the rat brain is capable of synthesizing and releasing DMT at concentrations similar to established monoamine neurotransmitters like serotonin [27], the possibility that DMT is an authentic neurotransmitter is still speculative. This issue has been controversial for decades [28] and requires the demonstration of an activity-dependent release (i.e., Ca2+-stimulated) of DMT at a synaptic cleft to be fully established in the human brain.}}</ref><ref name="AraújoCarvalhoBastosMde2015">{{cite journal | vauthors = Araújo AM, Carvalho F, Bastos Mde L, Guedes de Pinho P, Carvalho M | title = The hallucinogenic world of tryptamines: an updated review | journal = Arch Toxicol | volume = 89 | issue = 8 | pages = 1151–1173 | date = August 2015 | pmid = 25877327 | doi = 10.1007/s00204-015-1513-x | bibcode = 2015ArTox..89.1151A | url = }}</ref>