white → brown1
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Melatonin
N-Acetyl-5-methoxytryptamine
Circadin, Melatonine, Pineal hormone
Melatonin is an endogenous hormone and indoleamine compound naturally produced by the pineal gland in response to darkness, regulating sleep-wake cycles and circadian rhythms.1 First isolated and characterized by Aaron B. Lerner in 1958,2 it is widely available as an over-the-counter supplement for treating insomnia and promoting healthier sleep patterns.citation needed Beyond sleep regulation, melatonin functions as an antioxidant and influences mood, seasonal rhythms, and immune activity.1
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Light0.3-1 mg
Supplement products are available across a wide range, from 0.3 mg to 10 mg or more, and a prolonged-release 2 mg oral formulation is used medically. Doses of roughly 2-10 mg have been explored for circadian rhythm disruption such as jet lag; relatively large doses of 75-80 mg have been described as producing a more pronounced soporific effect. Administration after eating slows absorption and lowers peak concentrations. Alcohol may reduce the effects.
Duration
Onset1 hour
Total6-8 hours
Half-life
20-50 minutes
Subjective Effects
Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.
Melatonin produces a subtle shift toward sleepiness rather than a distinct intoxication, and at typical low doses it is often indistinguishable from placebo. Its primary action is to shorten the time taken to fall asleep rather than to sedate outright, and it is described as a sleep catalyst at modest doses that only becomes genuinely soporific at much larger ones. Reports from recreational contexts note that it is not particularly hypnotic when used to close out a drug experience. Residual drowsiness can carry into the following day, though large doses have been described as producing increased total sleep without hangover.
Physical
The dominant physical effect is drowsiness accompanied by a lowering of body temperature; headache, dizziness, mild tremor, abdominal cramps, and nausea are also reported.
Uncomfortable
Cognitive
Reduced alertness, confusion, and mild anxiety have been reported, alongside transient depressive symptoms and irritability.
Emotional
Impairment
Pharmacology
Pharmacodynamics
Melatonin acts as a potent full agonist at melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2), both G protein-coupled receptors of the Gi/o subtype, with MT1 also exhibiting Gq coupling.citation needed MT1 receptor activation inhibits adenylyl cyclase, reducing cyclic AMP formation and downstream protein kinase A activity,3 while also activating phospholipase C and modulating ion channel flux.citation needed MT2 receptor activation similarly inhibits adenylyl cyclase and guanylyl cyclase while increasing protein kinase C activity. These receptors are expressed throughout the central nervous system, including the suprachiasmatic nucleus responsible for circadian rhythm regulation, as well as in peripheral tissues including the retina, cardiovascular system, and immune cells.
Beyond receptor-mediated effects, melatonin functions as a high-capacity free radical scavenger within mitochondria, directly neutralizing reactive oxygen and nitrogen species while promoting expression of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase through receptor-triggered signal transduction pathways.citation needed
Pharmacokinetics
Melatonin absorption and bioavailability vary widely between individuals.citation needed It is hepatically metabolized primarily by CYP1A2, with lesser contributions from CYP1A1, CYP2C19, and CYP1B1. The primary metabolic pathway transforms melatonin into 6-hydroxymelatonin, which is then conjugated with sulfate or glucuronide and excreted in urine.2 Immediate-release formulations cause blood levels to peak in approximately one hour.citation needed
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
1,2-BenzodiazepineAbametapirAbataceptAbirateroneAcenocoumarol
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Full Tolerance
In adults with primary insomnia, sleep benefits from 2 mg prolonged-release melatonin taken nightly were maintained or enhanced over six months with no signs of tolerance in a randomized placebo-controlled trial. A prospective open-label extension likewise found no evidence of tolerance during 6-12 months of treatment. These findings are specific to 2 mg prolonged-release melatonin in the studied adult insomnia populations and do not establish tolerance behavior for immediate-release products, other doses, or other indications.
Harm Potential
Addiction & Dependence
Psychological
Extremely LowNo evidence of psychological addiction or abuse potential has been documented.citation needed Melatonin is not associated with compulsive use patterns or reinforcing effects.
Physical
Extremely LowNo physical dependence or withdrawal syndrome has been reported with melatonin use.citation needed
Toxicity
Endocrine/Reproductive
High doses may inhibit ovulation and could potentially affect gonadal development in individuals under 20 years of age, as melatonin levels are inversely related to gonadal maturation during development.citation needed
Psychosis Risk
Transient mild anxiety, confusion, and irritability have been reported as uncommon side effects,citation needed but these occur at similar frequencies to placebo. No psychotic episodes have been documented.
History & Culture
Discovery and Isolation
The discovery of melatonin traces back to early twentieth-century research on skin pigmentation in amphibians. In 1917, Carey Pratt McCord and Floyd P. Allen observed that feeding extracts from bovine pineal glands to tadpoles caused their skin to lighten through contraction of dark epidermal…
Legality
International
Melatonin does not appear in the schedules of the 1961 Single Convention, the 1971 Convention on Psychotropic Substances, or the tables of the 1988 Convention.
By Country
Controlled / restricted3
ThailandRestrictedMinistry of Public Health Notification Re: Dangerous Drugs, dated 26 May B.E. 2521 (1978), item 264041
Melatonin is classified in Thailand as a dangerous drug under the Ministry of Public Health notification covering sedatives and hypnotics that are not separately classified as specially controlled drugs or psychotropic substances. The Thai Food and Drug Administration applies this classification to melatonin and treats melatonin found in food supplements as a modern drug adulterant rather than a permitted food ingredient.
TurkeyRestrictedTurkey’s Ministry of Agriculture and Forestry lists melatonin in the Takviye Edici Gıdalar Kısıtlı Maddeler Listesi. The list states that melatonin is not considered suitable for use as an active ingredient in food supplements, pursuant to a decision of the Tenth Chamber of the Council of State in case 2022/7193.
Prescription9
AustriaPrescription onlyAustria’s Rezeptpflichtverordnung lists MELATONIN in Annex A, Part 2 for human medicines, with the designation RP (rezeptpflichtig, prescription-only). Prescription-only medicines may be supplied only on the prescription of an authorised prescriber and, apart from specified wholesale channels, may only be kept for supply, offered, or supplied in pharmacies; the melatonin entry was inserted by BGBl. II Nr. 183/2009, published on 23 June 2009.
GermanyPrescription onlyArzneimittelverschreibungsverordnung, Anlage 113
Melatonin is listed in Germany's prescription-medicine ordinance, subject to the ordinance's stated exceptions. Products outside an applicable exception require a prescription.
IrelandPrescription only
JapanPrescription onlyMelatonin is supplied in Japan as the approved medicine Melatobel and is classified as a prescription drug (処方箋医薬品). The PMDA-approved electronic package insert identifies melatonin as its active ingredient and states that it is to be used on a physician's or other authorized prescriber's prescription. Article 49 of the Pharmaceuticals and Medical Devices Act prohibits pharmacy operators and medicine sellers from selling or providing a medicine designated by the Minister of Health, Labour and Welfare to a person who has not received a prescription, absent a legitimate reason.
New ZealandPrescription only
South KoreaPrescription onlyThe Ministry of Food and Drug Safety lists Dreamel PR Tablet 2 mg, whose active ingredient is melatonin, as an authorised prescription medicine in South Korea. Its supply is subject to the prescription-medicine classification.
SwedenPrescription onlyMelatonin is supplied in Sweden as a prescription-only medicinal product. The Swedish Medical Products Agency classifies the authorised product Melatonin 2care4 3 mg tablett as prescription-only, so it is dispensed on prescription rather than as an over-the-counter medicine. Swedish classification is made at package level when a medicine is authorised for sale.
SwitzerlandPrescription onlyOrdinance on Medicinal Products (VAM; SR 812.212.21), together with Swissmedic's official classification of melatonin products3839
Melatonin products in Switzerland are placed on the market only as medicinal products. Authorised melatonin products are available only on prescription; Swissmedic attributes this treatment to their pharmacological effect and potential risks.
Legal / decriminalized5
Czech RepublicLegal (regulated)Czech law requires the State Institute for Drug Control to classify each registered human medicinal product for prescription or non-prescription supply. Melatonin therefore has product-specific medicine controls: the SÚKL register classifies Melatonin Vitabalans 3 mg, 10-tablet pack as non-prescription (OTC), while the 30-tablet pack is prescription-only (Rx).
IndonesiaLegal (regulated)Keputusan Kepala Badan Pengawas Obat dan Makanan Nomor HK.02.02.1.2.12.20.1417 Tahun 2020 tentang Penetapan dan Pengawasan Melatonin sebagai Suplemen Kesehatan untuk Keperluan Khusus141516
Melatonin is regulated in Indonesia as a health supplement for special purposes under a 2020 decision of the Food and Drug Authority (BPOM). The decision limits the daily dose to 0.5 mg and subjects melatonin products to BPOM's special-purpose health-supplement framework rather than Indonesia's narcotics or psychotropics schedules.
NorwayLegal (regulated)Direktoratet for medisinske produkter, Klassifisering av melatonin25
In Norway, melatonin products with a recommended daily dose of no more than 1 mg and an intended use consistent with EFSA-approved health claims are not necessarily medicines. Such products may be marketed as food supplements, but must comply with the Food Act and its regulations; the Directorate for Medical Products has also told customs not to detain these low-dose products in private importation.
RussiaLegal (regulated)In Russia, the State Register of Medicines records a 3 mg film-coated melatonin tablet under registration certificate ЛП-№(009707)-(РГ-RU). The registered packs are supplied without a prescription. The record identifies melatonin as the active substance and lists the product as a medicinal preparation.
SpainLegal (regulated)Melatonin is regulated as an authorised medicine in Spain. The AEMPS CIMA record for Melatonina Noxarem 3 mg comprimidos identifies melatonin as its active substance and classifies the product as available without prescription; the record also shows that it is commercially available. Spain's medicines law requires the AEMPS to classify each authorised medicine as either subject to medical prescription or not subject to medical prescription.
Not scheduled1
United StatesNot scheduledAvailable over-the-counter as a dietary supplement rather than a regulated medication.12 The FDA has granted orphan drug status for prescription formulations treating circadian rhythm disorders in blind individuals, but the compound itself remains unscheduled and widely accessible without prescription.12
References
Source Pages
Citations
- Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders. (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC9907215/12
- Melatonin: Pharmacology, Functions and Therapeutic Benefits. (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC5405617/12
- MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective. (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC5091650/1
- Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician's perspective. (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC6362935/1
- Rezeptpflichtverordnung (BGBl. Nr. 475/1973), Anlage A, Teil 2 human. ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/Dokumente/Bundesnormen/NOR40273195/NOR40273195.html1
- Rezeptpflichtverordnung (BGBl. Nr. 475/1973), Anlage A, Teil 2 human. ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=100103511
- Rezeptpflichtverordnung (BGBl. Nr. 475/1973), Anlage A, Teil 2 human. ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/Dokumente/BgblAuth/BGBLA_2009_II_183/BGBLA_2009_II_183.html1
- Act No. 378/2007 Coll., on Medicinal Products, § 39; SÚKL Database of Medicinal Products. e-sbirka.gov.cz (n.d.). https://e-sbirka.gov.cz/sb/2007/3781
- Act No. 378/2007 Coll., on Medicinal Products, § 39; SÚKL Database of Medicinal Products. prehledy.sukl.cz (n.d.). https://prehledy.sukl.cz/prehledy/v1/dlp/02492321
- Act No. 378/2007 Coll., on Medicinal Products, § 39; SÚKL Database of Medicinal Products. prehledy.sukl.cz (n.d.). https://prehledy.sukl.cz/prehledy/v1/dlp/02492331
Further Reading
Article Status
Step 1 · Automated synthesisAn autonomous workflow built by Josie Kins compiled this article's foundation from information published across the web.
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Recent changes7 human edits · latest
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24 January 2026
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
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