Editing Serotonin (section)

==Effects in humans==
Serotonin, given [[oral administration|orally]] at a dose of 100{{nbsp}}mg, produced effects in humans including [[blood pressure]] changes, [[abdominal cramp]]s, [[muscle ache]]s, and a feeling of [[sedation]].<ref name="McKennaTowers1984">{{cite journal | vauthors = [[Dennis McKenna|McKenna DJ]], Towers GH | title = Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview | journal = J Psychoactive Drugs | volume = 16 | issue = 4 | pages = 347–358 | date = 1984 | pmid = 6394730 | doi = 10.1080/02791072.1984.10472305 | url = https://bitnest.netfirms.com/external/10.1080/02791072.1984.10472305 | quote = Table III: Orally and Parenterally Active Psychotropic Tryptamine Derivatives* [...] Name of Compound: Serotonin [...] Dosage (mg): 100#. Route: Oral. [...] # Cardiovascular and autonomic symptoms; little central activity.}}</ref><ref name="KantorDudlettesShulgin1980">{{cite journal | vauthors = Kantor RE, Dudlettes SD, Shulgin AT | title = 5-Methoxy-α-Methyltryptamine (α,O-Dimethylserotonin), A Hallucinogenic Homolog of Serotonin | journal = Biol Psychiatry | volume = 15 | issue = 2 | pages = 349–352 | date = April 1980 | pmid = 7417623 | doi = | url = https://bitnest.netfirms.com/external/Biol.Psychiatry/15.2.349 | quote = Table I. Human Potency of the Hallucinogenic Tryptamines [...] Name: Serotonin. Dosage: 100<sup>c</sup>. Route: Oral. Reference: Murphree et al., 1960. [...] <sup>c</sup> Largely cardiovascular and autonomic distress.}}</ref><ref name="MurphreeJenneyPfeiffer1960">{{cite journal | vauthors = Murphree HB, Jenney EH, Pfeiffer CC | title = Comparison of the Effects of Congeners of Lysergic Acid Diethylamide and Tryptophane in Normal Volunteers | journal = Pharmacologist | volume = 2 | issue = 2 | pages = 64 | url = https://bibliography.maps.org/resources/download/9620 | archive-url = https://web.archive.org/web/20250407090049/https://bibliography.maps.org/resources/download/9620 | archive-date = 7 April 2025 | quote = [...] Comparison was made in normal human volunteers of the effects of [...] 5-hydroxytryptamine [...] with [LSD]. The subjects were highly trained to recognize the effects of [LSD] and other hallucinogens. All compounds were given orally. [...] 5-hydroxytryptamine in a dose of 100 mg produced a fall in systolic and a rise in diastolic blood pressures together with a feeling of sedation, abdominal cramping, and muscle aching similar to those of [LSD]. Effects were delayed 6 to 8 hours after dosage. [...]}}</ref> In contrast to psychedelic drugs like [[LSD]], no [[hallucinogen]]ic effects were reported.<ref name="McKennaTowers1984" /><ref name="KantorDudlettesShulgin1980" /><ref name="MurphreeJenneyPfeiffer1960" /> In other studies, serotonin, at low [[intravenous injection|intravenous]] doses of 2 to 6{{nbsp}}mg, had no effects on [[electroencephalogram]] (EEG) readings in humans.<ref name="Erspamer1961" /> In accordance with the preceding findings, it has been stated that administration of serotonin in humans produces no [[psychoactive drug|psychoactive]] effects that cannot be attributed to [[anxiety]] by its profound [[peripheral nervous system|peripheral]] [[adverse effect]]s including [[cardiovascular disorder|circulatory disturbance]], other [[autonomic nervous system|autonomic]] effects, and [[vomiting]].<ref name="Erspamer1961">{{cite book | last=Erspamer | first=V. | title=Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des Recherches Pharmaceutiques | chapter=Recent Research in the Field of 5-Hydroxytryptamine and Related Indolealkylamines | journal=Fortschritte der Arzneimittelforschung. Progress in Drug Research. Progres des Recherches Pharmaceutiques | publisher=Birkhäuser Basel | publication-place=Basel | date=1961 | volume=3 | isbn=978-3-0348-7043-6 | doi=10.1007/978-3-0348-7041-2_3 | pages=151–367 | pmid=13890703 | quote = 13.9 Indolealkylamines and the CNS in human beings 13.91 Central effects of 5-HT [...]}}</ref><ref name="Marrazzi1957">{{cite journal | vauthors = Marrazzi AS | title = The effects of certain drugs on cerebral synapses | journal = Ann N Y Acad Sci | volume = 66 | issue = 3 | pages = 496–507 | date = March 1957 | pmid = 13425238 | doi = 10.1111/j.1749-6632.1957.tb40745.x | bibcode = 1957NYASA..66..496M | url = | quote = Unfortunately, except for the intraventricular injections described by Sherwood,7 there have been, thus far, no documented reports of serotonin-induced mental disturbance* in man that are clearly separable from the natural anxiety initiated by the profound peripheral effects such as circulatory disturbance, other autonomic effects, and emesis. [...] 7. SHERWOOD, S, L. 1955. The responses of psychotic patients to intraventricular injections. Proc. Roy. Soc. Med. 48: 855.}}</ref> [[Intracerebroventricular injection]] of serotonin has been studied in patient with severe [[psychiatric disorder|psychiatric condition]]s, but little information about its psychoactive effects is provided.<ref name="Marrazzi1957" /><ref name="FeldbergSherwoodRichter1955">{{cite journal | vauthors = Feldberg W, Sherwood SL, Richter D | title = Recent experiments with injections of drugs into the ventricular system of the brain: The Response of Psychotic Patients to Intraventricular Injections | journal = Proc R Soc Med | volume = 48 | issue = 10 | pages = 853–864 | date = October 1955 | pmid = 13266838 | pmc = 1919229 | doi = 10.1177/003591575504801031| url = | quote = Serotonin. [...] 4 patients received this drug in doses of 15 to 75 μg. [...]}}</ref>

It is thought that [[exogenous]] serotonin is too [[hydrophilic]] to cross the [[blood–brain barrier]] and has too poor of [[metabolic stability]] due to rapid [[drug metabolism|metabolism]] by [[monoamine oxidase]] (MAO) such that it cannot produce [[drug]]-like [[central nervous system|central]] effects in humans with [[peripheral administration]].<ref name="KantorDudlettesShulgin1980" /><ref name="TiHKAL1997">{{cite book | author1 = [[Alexander T. Shulgin]] | author2 = [[Ann Shulgin]] | title = TiHKAL: The Continuation | publisher = Transform Press | date = 1997 | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-9-2 | oclc = 38503252 | url = https://books.google.com/books?id=jl_ik66IumUC | access-date = 30 January 2025 | quote = Two obstacles effectively prohibit this availability. Serotonin has a free hydroxy group (the 5-hydroxy which is the H of 5-HT). This is a big polar water-loving pimple which denies it any passage across the brain’s defensive Maginot Line, the blood-brain barrier. And there is the second problem. There is a exposed amino group, the amine of T of 5-HT, the tryptamine, which is immediately removed by the body’s monoamine oxidase enzyme. In short, it is blocked from entry into the brain because it is both too polar and too metabolically fragile.}}</ref> However, close [[structural analog|analogue]]s of serotonin that are more [[lipophilic]] and [[metabolic stability|metabolically stable]], like [[bufotenin]] (''N'',''N''-dimethylserotonin), [[5-MeO-DMT]] (''N'',''N'',''O''-trimethylserotonin), and [[5-MeO-AMT]] (α,''O''-dimethylserotonin), among many others, are active and produce pronounced centrally mediated effects in humans.<ref name="TiHKAL1997" /><ref name="AraújoCarvalhoBastos2015">{{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 = https://psilosybiini.info/paperit/The%20hallucinogenic%20world%20of%20tryptamines,%20an%20updated%20review%20(Ara%FAjo%20et%20al.,%202015).pdf}}</ref> These drugs are [[binding selectivity|non-selective]] [[serotonin receptor agonist]]s like serotonin and are [[serotonergic psychedelic]]s due to activation of the serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]].<ref name="TiHKAL1997" /><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = | doi-access = free }}</ref><ref name="AraújoCarvalhoBastos2015" /> [[α-Methylserotonin]] is well-studied in [[preclinical research]], but is not known to have been tested in humans.<ref name="TiHKAL1997" />