|Summary sheet: Melatonin|
|Routes of Administration|
N-Acetyl-5-methoxytryptamine (also known as melatonin) 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; it may have different functions in other organisms.
Melatonin is commonly used as a medication for insomnia; however, there is insufficient scientific evidence to prove any benefit in this area. 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.
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. Where many tryptamines have a group bonded to the ethylamine, melatonin has an acetyl group.
Disclaimer: The effects listed below are taken from the subjective effect index, which is based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy degree of skepticism. It is worth noting that these effects will rarely (if ever) occur all at once, although higher doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
- Sedation - Melatonin does not produce sedation in the manner of central nervous depressants like alcohol, benzodiazepines, or zolpidem.
- Muscle relaxation - In comparison to other compounds, such as benzodiazepines, this effect is very mild and only present at heavy dosages.
- Decreased libido - This effect can be caused by the Sedation or by the fact that melatonin can inhibit secretion of hormones that control sexual functions.
- Sleepiness - Regarding its effects on the user's physical energy levels, melatonin is commonly considered to facilitate sleepiness. It is often used and sold as a sleep aid and mimics one's natural circadian cycle.
- Dream potentiation - Melatonin is extremely effective at increasing the duration, occurrence, and vividness of dreams. It is very common for people to note that their dreams had noticeably increased the morning after ingesting melatonin as a sleep aid. Melatonin is sometimes used to increase the chances of lucid dreaming.
- Depersonalization - Depersonalization can present itself upon the come-up and persist well into the next day if the user has ingested a massive dose.
- Irritability Irritability is only present at high dosages when the user resists the urge to sleep.
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. Prolonged-release melatonin is safe with long-term use of up to 12 months.
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.
- Canada: Melatonin is freely available to purchase as a dietary supplement and can be found at most pharmacies and grocery stores across the country.
- Germany: Melatonin is a prescription medicine, according to Anlage 1 AMVV.
- India: Melatonin is legal to purchase as a dietary supplement.
- Italy: Melatonin is legal to purchase as a dietary supplement.
- Switzerland: Melatonin can only be obtained with a medical prescription. 
- United Kingdom: Melatonin is a licensed prescription-only medicine (POM) in the United Kingdom. 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.
- 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.
- DeMuro, R. L., Nafziger, A. N., Blask, D. E., Menhinick, A. M., & Bertino, J. S. (2000). The absolute bioavailability of oral melatonin. The Journal of Clinical Pharmacology, 40(7), 781-784. https://doi.org/10.1177/00912700022009422
- Melatonin | http://www.sleepdex.org/melatonin.htm
- Melatonin. | https://www.ncbi.nlm.nih.gov/pubmed/16219483
- Management of Insomnia Disorder [Internet]. | https://www.ncbi.nlm.nih.gov/pubmed/26844312
- Phase-dependent treatment of delayed sleep phase syndrome with melatonin | http://www.ncbi.nlm.nih.gov/pubmed/16295212
- Tihkal MELATONIN | https://erowid.org/library/books_online/tihkal/tihkal35.shtml
- Melatonin, a potential therapeutic agent for smooth muscle related pathological conditions and aging (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/20939818
- Melatonin mediates two distinct responses in vascular smooth muscle (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/20939818
- Melatonin Side Effects (EverydayHealth) | http://www.everydayhealth.com/drugs/melatonin
- The Efficacy and Safety of Exogenous Melatonin for Primary Sleep Disorders | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490287/
- Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370968/
- Melatonin prolonged release: in the treatment of insomnia in patients aged ≥55 years. | https://www.ncbi.nlm.nih.gov/pubmed/23044640
- Circadin® 2 mg Retardtabletten sind in Apotheken nur gegen ärztliche Verschreibung erhältlich. | https://compendium.ch/mpub/pnr/1141302/html/de
- "Medicines Act 1968 Section 13".