Melatonin
A hormone produced by the pineal gland that regulates the sleep-wake cycle. Exogenous melatonin is the most widely used sleep supplement worldwide. For nootropic purposes, sleep is foundational — poor sleep destroys cognitive performance more than any supplement can compensate for. Low doses (0.3-1 mg) are often more effective than the common 5-10 mg doses sold commercially.
Dosage
Optimal sleep dose: 0.3-1 mg taken 30-60 minutes before bed. Commercial doses of 3-10 mg are higher than needed and can cause next-day grogginess. Extended-release forms help with sleep maintenance (waking in the middle of the night).
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
40-60 minutes
Administration
Oral (tablets, capsules, gummies, sublingual). Sublingual provides faster onset.
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Mechanism of Action
Melatonin binds to G-protein-coupled MT1 and MT2 receptors, which are densely expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus—the brain's master circadian pacemaker. MT1 activation couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP, which suppresses SCN neuronal firing and promotes sleepiness. MT2 activation modulates cGMP signaling and phase-shifts the circadian rhythm (useful for jet lag and shift work). Melatonin also has direct antioxidant properties, scavenging hydroxyl and peroxyl radicals in mitochondria and upregulating antioxidant enzymes like glutathione peroxidase. It supports immune function through modulation of T-cell cytokine production and may act at MT3 (quinone reductase 2) binding sites. Low doses are often more effective because they mimic physiological nighttime levels.
Regulatory Status
Over-the-counter dietary supplement in the US, Canada, and some other countries. Prescription-only in the EU, UK, Australia, and Japan.
Risks & Safety
Common
Morning grogginess (especially at high doses), vivid dreams, mild headache.
Serious
May worsen symptoms in people with autoimmune conditions. Interacts with blood thinners, diabetes medications, and immunosuppressants.
Rare
Depression, daytime sleepiness, reduced sex drive with chronic high-dose use.
Compare Melatonin With
Research Papers
10Published: April 19, 2015
AI Summary
Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Great advances in this field could be achieved by developing multicentre trials in a large series of patients, in order to establish efficacy of melaton...
Published: February 1, 2021
AI Summary
Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD.
Published: October 15, 2015
AI Summary
As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress.
Published: August 7, 2023
AI Summary
Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there.
Published: February 25, 2018
AI Summary
Melatonin anticancer activity is mediated by interfering with various cancer hallmarks. The studies discussed in this review should serve as a solid foundation for researchers and physicians to support basic and clinical studies on melatonin as a promising anticancer agent.
Published: January 1, 2021
AI Summary
Melatonin is a multifunctional biomolecule found in both animals and plants. With a reduced anabolic capacity for melatonin biosynthesis and an increased catabolic capacity for melatonin metabolism, all plants generally maintain low melatonin levels.
Published: April 30, 2024
AI Summary
This review consolidates the accumulating evidence on melatonin's multifaceted protective effects in different pathological contexts. Furthermore, melatonin's protective effects are suggested to be mediated by interactions with its receptors, estrogen receptors and other nuclear receptors.
Published: March 2, 2019
AI Summary
These include light exposure and photoreceptor contributions in melatonin suppression, leading to consideration of how blue blockers, cataract, and light therapy might affect sleep and mood in patients. Additionally, the interactions between melatonin, sleep and refractive error development are discussed.
Published: January 10, 2021
AI Summary
These low quantities, within a dietary intake, are enough to reach significant plasma concentrations of melatonin, and are thus able to exert beneficial effects. Melatonin has demonstrated antioxidant, anticarcinogenic, immunomodulatory and neuroprotective actions.
Published: October 4, 2020
AI Summary
Inspection of approximately 80 publications in the field revealed that most melatonergic ligands were structural analogues of melatonin combining three essential features of the parent compound: an aromatic ring bearing a methoxy group and an amide side chain in a relative arrangement similar to that present in melatonin.
Frequently Asked Questions
What is Melatonin used for?
A hormone produced by the pineal gland that regulates the sleep-wake cycle. Exogenous melatonin is the most widely used sleep supplement worldwide. For nootropic purposes, sleep is foundational — poor sleep destroys cognitive performance more than any supplement can compensate for. Low doses (0.3-1 mg) are often more effective than the common 5-10 mg doses sold commercially.
What are the side effects of Melatonin?
Common: Morning grogginess (especially at high doses), vivid dreams, mild headache. Serious: May worsen symptoms in people with autoimmune conditions. Interacts with blood thinners, diabetes medications, and immunosuppressants. Rare: Depression, daytime sleepiness, reduced sex drive with chronic high-dose use.
How is Melatonin administered?
Melatonin is administered via oral (tablets, capsules, gummies, sublingual). sublingual provides faster onset..
What is the half-life of Melatonin?
The half-life of Melatonin is 40-60 minutes.
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