Melatonin

Summary sheet: Melatonin

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. ⇣ Oral Dosage Bioavailability 15% - 15% Threshold 0.25 mg Light 0.5 - 1 mg Common 1 - 3 mg Strong 3 - 6 mg Heavy 6 mg + Duration 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.
Interactions

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 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. 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.

Chemistry

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.

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

Pharmacology

This pharmacology section is incomplete. You can help by adding to it.

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). Melatonin receptors 1 and 2 are both G_i/o-coupled GPCRs, although melatonin receptor 1 is also G_q-coupled. 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.
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. 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).

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

• • 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.
    • Physical euphoria - This effect can occur alongside Muscle relaxation, and is only present at heavy dosages when the user resists the urge to sleep.
  • 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.

Cognitive effects

• • 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.
  • Anxiety Suppression or Anxiety - Although this substance decreases anxiety with most people, it can also cause anxiety by some.
  • 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.

After effects

• • Headaches - A small subset of people may experience headaches the day after ingesting melatonin.
  • Sleepiness

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:

• Erowid Experience Vaults: Melatonin

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.

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.
• 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. It is however available as a dietary supplement in certain forms, often in low dosages or as combination preparations.
• India: Melatonin is legal to purchase as a dietary supplement.
• Italy: Melatonin is legal to purchase as a dietary supplement.
• Ireland: Melatonin is a prescription-only medicine.
• Sweden: Melatonin is an over-the-counter medication in small amounts, but generally a prescription pharmaceutical.
• Switzerland: Melatonin is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a 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.

See also

• Responsible use
• Oneirogen
• Neurotransmitter
• Hormone
• Tryptamine

External links

• Melatonin (Wikipedia)
• Melatonin as a medication and supplement (Wikipedia)
• Melatonin (Erowid Vault)
• Melatonin (TiHKAL / Isomer Design)
• Melatonin (DrugBank)
• Melatonin (Drugs.com)
• Melatonin (Examine)