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Summary sheet: Melatonin
Chemical Nomenclature
Common names Melatonin
Substitutive name N-Acetyl-5-methoxytryptamine
Systematic name N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
Class Membership
Psychoactive class Oneirogen
Chemical class Tryptamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Bioavailability 15% - 15%[1]
Threshold 0.25 mg
Light 0.5 - 1 mg
Common 1 - 3 mg
Strong 3 - 6 mg
Heavy 6 mg +
Total 6 - 10 hours
Onset 5 - 20 minutes

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.


N-Acetyl-5-methoxytryptamine (also known as melatonin[2]) is a hormone of the tryptamine class. It is found in animals, plants, fungi, and bacteria. In animals, it functions as a hormone that anticipates the daily onset of darkness;[3] it may have different functions in other organisms.

Melatonin is active and can be taken sublingually and buccaly by placing it into one's mouth and allowing it to absorb over a period of 15-25 minutes. It is less active when taken orally.

Melatonin is commonly used as a medication for insomnia; however, there is insufficient scientific evidence to prove any benefit in this area.[4] It is sold over-the-counter in most pharmacies within the United States and Canada. In other countries, it may require a prescription or not be available.

It should be noted that when purchasing melatonin, dosages may range from 3 - 10mg. While not dangerous, this dosage range is well beyond the effective dose of .25 mg, and may increase instances of drowsiness the next day.[5]


Melatonin is comprised of a monoamine chain attached to an indole ring at the third carbon. A monoamine chain is made up of an amine group attached to an ethane chain. This monoamine chain can be found in many neurotransmitters, including histamine, dopamine, adrenaline, and noradrenaline. It is also found in many psychoactive substances such as members of the tryptamine and phenethylamine chemical classes.

Melatonin, being a tryptamine, shares many structural properties with psychedelic substances. However, it lacks their associated psychedelic effects.[6] Where many tryptamines have a group bonded to the ethylamine, melatonin has an acetyl group.

Melatonin can reacted when used with Erlich reagent turning pink/red to purple (Tested with Natrol Melatonin Tablet).


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Melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar binding affinity), both of which belong to the class of G-protein coupled receptors (GPCRs).[7] Melatonin receptors 1 and 2 are both Gi/o-coupled GPCRs, although melatonin receptor 1 is also Gq-coupled.[7] Melatonin also acts as a high-capacity free radical scavenger within mitochondria which also promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase via signal transduction through melatonin receptors.[7]
Melatonin is metabolized in the liver by cytochrome P450 enzyme CYP1A2 to 6-hydroxymelatonin. Metabolites are conjugated with sulfuric acid or glucuronic acid for excretion in the urine. 5% of melatonin is excreted in the urine as the unchanged drug.[8] Some of the metabolites formed via the reaction of melatonin with a free radical include cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK).[7]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

Cognitive effects

After effects
Aftereffects (3).svg

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Toxicity and harm potential

Melatonin is non-addictive, not known to be harmful, and has an extremely low toxicity relative to dose. Similar to other tryptamines, there are relatively few physical side effects associated with acute melatonin exposure. Various studies have shown that in reasonable doses in a careful context, it presents no negative cognitive, psychiatric, or toxic physical consequences.

Melatonin appears to cause very few side effects as tested in the short-term (up to three months) at low doses. Two systematic reviews found no adverse effects of melatonin usage in several clinical trials, while comparative trials found the adverse effects headaches, dizziness, nausea, and drowsiness were reported about equally for both melatonin and placebo.[11][12] Prolonged-release melatonin is safe with long-term use of up to 12 months.[13]

Lethal dosage

The median lethal dose of melatonin at which 50% of participants die (LD50) for human beings has never been reached in any setting.

Dependence and abuse potential

Melatonin is not habit-forming. It is possible, however, to develop a mild physical dependency if this compound is used on a nightly basis for a prolonged period. This simply means that if one suddenly stops their usage of the substance without tapering, they may have trouble sleeping for a couple of days afterward.

Tolerance to the effects of melatonin is slowly built after prolonged and repeated usage. After that, it takes about 7 days for the tolerance to be reduced to half and 14 days to be back at baseline (in the absence of further consumption). Melatonin presents cross-tolerance with no other known compounds, meaning that after the use of melatonin, other psychoactive compounds will not have a reduced effect.

Legal status

  • Australia: Melatonin is schedule 4 (prescription only) except when included in schedule 3 (pharmacist only) for human use:
    • in modified release tablets containing 2 mg or less of melatonin for monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep for adults aged 55 or over, in packs containing not more than 30 tablets.[14]
  • Canada: Melatonin is freely available to purchase as a dietary supplement and can be found at most pharmacies and grocery stores across the country.[citation needed]
  • Germany: Melatonin is a prescription medicine, according to Anlage 1 AMVV.[15] It is however available as a dietary supplement in certain forms, often in low dosages or as combination preparations.[16]
  • India: Melatonin is legal to purchase as a dietary supplement.[citation needed]
  • Italy: Melatonin is legal to purchase as a dietary supplement.[citation needed]
  • Sweden: Melatonin is an over-the-counter medication in small amounts, but generally a prescription pharmaceutical.[17]
  • Switzerland: Melatonin is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.[citation needed]
  • United Kingdom: Melatonin is a licensed prescription-only medicine (POM) in the United Kingdom.[citation needed] It is not a criminal offense to possess this medicine without a valid prescription. This medicine can legally be obtained with a valid prescription or through legal import of the medicine for personal use as outlined in Section 13 of the Medicines Act 1968.[18]
  • United States: Melatonin is listed as an uncontrolled substance and is legal to possess and distribute, and is freely available to purchase as a dietary supplement.[citation needed]

See also

External links


  1. DeMuro, R. L., Nafziger, A. N., Blask, D. E., Menhinick, A. M., Bertino, J. S. (July 2000). "The Absolute Bioavailability of Oral Melatonin". The Journal of Clinical Pharmacology. 40 (7): 781–784. doi:10.1177/00912700022009422. ISSN 0091-2700. 
  2. Sleepdex: Melatonin 
  3. Hardeland, R., Pandi-Perumal, S. R., Cardinali, D. P. (March 2006). "Melatonin". The International Journal of Biochemistry & Cell Biology. 38 (3): 313–316. doi:10.1016/j.biocel.2005.08.020. ISSN 1357-2725. 
  4. Brasure, M., MacDonald, R., Fuchs, E., Olson, C. M., Carlyle, M., Diem, S., Koffel, E., Khawaja, I. S., Ouellette, J., Butler, M., Kane, R. L., Wilt, T. J. (2015). Management of Insomnia Disorder. AHRQ Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality (US). 
  5. Mundey, K., Benloucif, S., Harsanyi, K., Dubocovich, M. L., Zee, P. C. (October 2005). "Phase-dependent treatment of delayed sleep phase syndrome with melatonin". Sleep. 28 (10): 1271–1278. doi:10.1093/sleep/28.10.1271. ISSN 0161-8105. 
  6. Erowid Online Books : “TIHKAL” - #35 MELATONIN 
  7. 7.0 7.1 7.2 7.3 JJockers, R., Delagrange, P., Dubocovich, M. L., Markus, R. P., Renault, N., Tosini, G., Cecon, E., Zlotos, D. P. (September 2016). "Update on melatonin receptors: IUPHAR Review 20". British Journal of Pharmacology. 173 (18): 2702–2725. doi:10.1111/bph.13536. ISSN 1476-5381. 
  8. Tordjman, S., Chokron, S., Delorme, R., Charrier, A., Bellissant, E., Jaafari, N., Fougerou, C. (April 2017). "Melatonin: Pharmacology, Functions and Therapeutic Benefits". Current Neuropharmacology. 15 (3): 434–443. doi:10.2174/1570159X14666161228122115. ISSN 1875-6190. 
  9. 9.0 9.1 Pozo, M. J., Gomez-Pinilla, P. J., Camello-Almaraz, C., Martin-Cano, F. E., Pascua, P., Rol, M. A., Acuña-Castroviejo, D., Camello, P. J. (2010). "Melatonin, a potential therapeutic agent for smooth muscle-related pathological conditions and aging". Current Medicinal Chemistry. 17 (34): 4150–4165. doi:10.2174/092986710793348536. ISSN 1875-533X. 
  10. Melatonin (Melatonin Time Release) - Side Effects, Interactions, Uses, Dosage, Warnings 
  11. Buscemi, N., Vandermeer, B., Hooton, N., Pandya, R., Tjosvold, L., Hartling, L., Baker, G., Klassen, T. P., Vohra, S. (December 2005). "The Efficacy and Safety of Exogenous Melatonin for Primary Sleep Disorders". Journal of General Internal Medicine. 20 (12): 1151–1158. doi:10.1111/j.1525-1497.2005.0243.x. ISSN 0884-8734. 
  12. Buscemi, N., Vandermeer, B., Hooton, N., Pandya, R., Tjosvold, L., Hartling, L., Vohra, S., Klassen, T. P., Baker, G. (18 February 2006). "Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis". BMJ : British Medical Journal. 332 (7538): 385–393. doi:10.1136/bmj.38731.532766.F6. ISSN 0959-8138. 
  13. Lyseng-Williamson, K. A. (November 2012). "Melatonin prolonged release: in the treatment of insomnia in patients aged ≥55 years". Drugs & Aging. 29 (11): 911–923. doi:10.1007/s40266-012-0018-z. ISSN 1179-1969. 
  14. Health, Poisons Standard February 2022 
  15. Anlage 1 AMVV - Einzelnorm 
  16. Moll, D. (2019), Melatonin in Nahrungsergänzungsmitteln 
  17. ”Receptfritt melatonin på apoteken”.
  18. "Medicines Act 1968 Section 13".