5-HTP can be manufactured and used as adrug and supplement with theINNTooltip International Nonproprietary Nameoxitriptan. Brand names include Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. As a drug, it is used in the treatment ofdepression and for certain other indications.
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]
5-HTP has been used medically and as a supplement under the nameoxitriptan in the treatment ofdepression and for certain other indications. As of 2025, there are no current FDA approved medications containing 5-HTP.
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 ofintracellular 5-HT2A receptors expressed incorticalneurons in themedial prefrontal cortex (mPFC) that lack theserotonin transporter (SERT) and are inaccessible to serotonin.[16][17] Serotonin itself is toohydrophilic to enter serotonergic neurons without the SERT, whereas serotonergic psychedelics and serotonin'sN-methylatedmetabolites andanalogues arelipophilic and readily enter these neurons.[16][17] These findings may also explain whyselective serotonin reuptake inhibitors (SSRIs) and related serotonergic agents do not produce psychedelic effects.[16]
The properties of 5-HTP in animaldrug discrimination tests have been studied.[18][19][20][21][22][23] 5-HTP generalizes with theserotonin releasing agentfenfluramine and its cue is markedly potentiated by theselective serotonin reuptake inhibitor (SSRI)fluoxetine.[18][19] However, numerousserotonin receptor antagonists, includingmethysergide,cyproheptadine,metergoline,methiothepin (metitepine),ketanserin,pirenperone,pizotifen, andmianserin, all failed to block the discriminative stimulus properties of 5-HTP.[18][19][20][21] Conflictingly however, in a subsequent study, pizotifen was able to fully block the discriminative stimulus properties of 5-HTP.[18][21] The inability of serotonin 5-HT2A receptor antagonists to block the discriminative stimulus properties of 5-HTP is in notable contrast to their ability to block the 5-HTP-induced HTR.[24] 5-HTP only partially substitutes for LSD in drug discrimination tests, whereas LSD andquipazine fully substitute for 5-HTP.[20] The full substitution of LSD and quipazine for 5-HTP can be blocked by the serotonin 5-HT2A receptor antagonist ketanserin.[20] The findings of drug discrimination tests suggest that 5-HTP has a more complex or compound discriminative stimulus compared to other agents like LSD and that its stimulus properties may not be readily explained by either the serotonin5-HT1 or5-HT2 receptors alone.[18][20][23] Instead, a combination of actions at these and/or other receptors may be involved in its stimulus effects.[18][20][23]
^abcTurner EH, Loftis JM, Blackwell AD (March 2006)."Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan".Pharmacology & Therapeutics.109 (3):325–338.doi:10.1016/j.pharmthera.2005.06.004.PMID16023217.S2CID2563606.5-HTP is commonly given to rats or mice to test the SSRI potency of putative antidepressants (O'Neil & Moore, 2003). This simple in vivo test measures the potency of a compound in potentiating the serotonin syndrome induced by the administration of 5-HTP (Grahame-Smith, 1971). The behavioral and physiological features of this syndrome include hypolocomotion, head twitch, forepaw treading, tremors, hindlimb abduction, flat body posture or hunched back, cyanosis, and hyperthermia. In rodents, 5-HTP induces a serotonin syndrome at dosages of 100– 200 mg/ kg (Casal et al., 2000; Nisijima et al., 2000, 2001; see Section 4.4.3 for more on serotonin syndrome).
^Bouchard S, Bousquet C, Roberge AG (September 1981). "Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat".Journal of Neurochemistry.37 (3):781–7.doi:10.1111/j.1471-4159.1982.tb12555.x.PMID6974228.S2CID43853143.
^Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H (May 2008). "Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat".The European Journal of Neuroscience.27 (9):2466–72.doi:10.1111/j.1460-9568.2008.06201.x.PMID18445233.S2CID18940166.
^Bouchard S, Roberge AG (July 1979). "Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat".Canadian Journal of Biochemistry.57 (7):1014–8.doi:10.1139/o79-126.PMID39668.
^Amamoto T, Sarai K (September 1976). "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".Hiroshima Journal of Medical Sciences.25 (2–3):135–40.PMID1088369.
^abcSchmid, Cullen L.; Bohn, Laura M. (2018). "βArrestins: Ligand-Directed Regulators of 5-HT2A Receptor Trafficking and Signaling Events".5-HT2A Receptors in the Central Nervous System. Cham: Springer International Publishing. pp. 31–55.doi:10.1007/978-3-319-70474-6_2.ISBN978-3-319-70472-2.
^abcdefghShahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Lotan A, Wolf G, Lerer B, Lifschytz T (November 2022)."Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications".Int J Mol Sci.23 (22) 14148.doi:10.3390/ijms232214148.PMC9698447.PMID36430623.HTR was first described in mice after administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP) [22], and has been further characterized by subsequent investigators [23–29]. Although extensive research has documented the effect of 5-HTP to induce HTR in rodents [30–33], psychedelic effects have not been reported at doses administered to humans [34]. [...] 5-HTP-induced HTR has previously described by multiple authors [30–33,48]. However, 5-HTP has not been reported to have psychedelic effects in humans [49]. Although, overdoses of compounds that increase serotonin release can result in serotonin syndrome, which may include hallucinations [50,51], classic psychedelic effects resembling those induced by tryptaminergic and other psychedelic drugs have not been reported. In our study, administration of 5-HTP at 150–250 mg/kg induced significant HTR. The implications of administering equivalent high doses of 5-HTP to humans are unknown. There are two instances of administering up to 3000 mg 5-HTP per os per day but not as a single dose. Such prolonged exposure that can result in tolerance effects [49].
^Hanks JB, González-Maeso J (January 2013)."Animal models of serotonergic psychedelics".ACS Chem Neurosci.4 (1):33–42.doi:10.1021/cn300138m.PMC3547517.PMID23336043.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
^abcBarrett RJ, Blackshear MA, Sanders-Bush E (1982). "Discriminative stimulus properties of L-5-hydroxytryptophan: behavioral evidence for multiple serotonin receptors".Psychopharmacology (Berl).76 (1):29–35.doi:10.1007/BF00430750.PMID6805004.
^abcdefCunningham KA, Callahan PM, Appel JB (January 1985). "Differentiation between the stimulus effects of l-5-hydroxytryptophan and LSD".Eur J Pharmacol.108 (2):179–186.doi:10.1016/0014-2999(85)90723-x.PMID3156756.
^abcFriedman R, Barrett RJ, Sanders-Bush E (1983). "Additional evidence that L-5-hydroxytryptophan discrimination models a unique serotonin receptor".Psychopharmacology (Berl).80 (3):209–213.doi:10.1007/BF00436154.PMID6137018.
^Witkin JM, Brady LS, Barrett JE (1988). "Antagonism by ketanserin of the behavioral effects of quipazine but not l-5-hydroxytryptophan in squirrel monkeys".Psychopharmacology (Berl).94 (3):302–305.doi:10.1007/BF00174679.PMID3128804.
^abcWinter JC, Rabin RA (July 1988). "A comparison of the discriminative stimulus properties of l-5-hydroxytryptophan in the presence of either citalopram or Ro 4-4602".Pharmacol Biochem Behav.30 (3):613–616.doi:10.1016/0091-3057(88)90073-1.PMID3264918.
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