Melatonin
A hormone the pineal gland releases after dark, sold unregulated in the US and licensed as a prescription medicine in Europe
Melatonin signals darkness rather than causing sleep, so its effects are modest and its best evidence is in people whose own production has fallen. It is an over-the-counter supplement in the US and a prescription drug in Europe.
What is it?
Melatonin is the body's darkness signal: the pineal gland releases it at night and the circadian system, through MT1 and MT2 receptors, reads it as a time cue. It is not a sedative. Production falls with age, which is where the licensed indication sits.
The prescription evidence is in older adults. In 354 people aged 55 to 80 with insomnia, three weeks of 2 mg prolonged-release melatonin improved sleep quality and morning alertness together against placebo. A second trial in 170 patients over 55 found the same and no withdrawal effect on stopping.
A 791-adult trial followed it for six months, testing who responds.
The clearest newer signal is delirium after surgery. Across 16 trials in older surgical patients, melatonin-type drugs cut postoperative delirium from 28.4% to 21.0%, with melatonin itself effective and ramelteon not. In older medical inpatients, though, a trial was stopped for futility because delirium was too rare to prevent.
Outside insomnia it is studied constantly and settles little; in 60 children aged 7 to 12, 3 mg nightly for a month improved sleep onset and duration. Pooled trials also show fewer migraine days, about 12 extra minutes of sleep in older adults with cognitive impairment, and no clear benefit on sleep in cancer. In children with cerebral palsy, 3 to 10 mg nightly added over an hour of sleep at 12 weeks.
It is not inert: in a 2026 crossover trial, 5 mg impaired glucose tolerance in carriers of a common diabetes risk variant. At high doses alongside other medicines it raised liver enzymes in a small multiple sclerosis trial.
Mechanism of Action
Melatonin is the pineal gland's night-time hormone; through MT1 and MT2 receptors it signals darkness to the circadian clock rather than acting as a sedative.
Circadian timing
It signals night to the body clock through MT1 and MT2 receptors.
Sleep in older adults
Production falls with age; prolonged-release 2 mg improved sleep quality and morning alertness in people over 55.
Glucose
5 mg impaired glucose tolerance in carriers of a common MTNR1B diabetes risk variant.
Published Research
These are the trials that describe melatonin, read from their PubMed abstracts: two in adults with insomnia and one in children.
Prolonged-release melatonin in people over 55
354 people aged 55 to 80 with insomnia took 2 mg prolonged-release melatonin or placebo for three weeks after a placebo run-in. The responder rate — sleep quality and morning alertness improving together — favoured melatonin, alongside Pittsburgh Sleep Quality Index measures.
Six months, and who responds
791 adults aged 18 to 80 with primary insomnia took placebo for two weeks, then prolonged-release melatonin or placebo for three weeks, with melatonin patients continuing to 26 weeks. The trial tested whether age or low melatonin output better predicts response.
In children aged 7 to 12
60 healthy children with insomnia were randomised to 3 mg of melatonin nightly or placebo for a month, both groups having been taught sleep hygiene. Sleep onset delay, duration, maintenance and sleep anxiety improved on melatonin.
Glucose tolerance and a diabetes gene
In a crossover trial in 21 healthy adults, 5 mg melatonin worsened glucose tolerance by 11.7% and cut early insulin secretion in carriers of the MTNR1B diabetes risk variant, but not in non-carriers.
Delirium in medical inpatients
A double-blind trial of 5 or 8 mg melatonin in older medical inpatients was stopped early for futility: delirium was rare (3.6% against 1.9%) and sleep, mortality and readmission did not differ.
Children with cerebral palsy
In a double-blind trial, 3 to 10 mg melatonin nightly increased total sleep time by 1.3 hours and shortened sleep onset by about 28 minutes against placebo at 12 weeks.
Liver enzymes at high dose
A trial of high-dose melatonin with ocrelizumab in multiple sclerosis was stopped after 3 of 4 treated patients developed raised liver enzymes, which resolved on stopping; all took other drugs sharing liver metabolism.
Before anaesthesia in children
In the MAGIC trial's economic analysis of 100 children, melatonin cost slightly less than midazolam before anaesthesia, with no clear difference in procedure success or quality of life.
Delirium after surgery
Across 16 randomised trials with 2,115 older surgical patients, melatonin-type drugs reduced postoperative delirium from 28.4% to 21.0% (risk ratio 0.72); melatonin itself was effective, ramelteon was not, and doses of 5 mg or more did better.
Migraine prevention
Across 9 randomised trials with 788 people, melatonin reduced headache days, attack duration and severity against placebo and raised the 50% response rate (risk ratio 1.38), but was generally less effective than amitriptyline.
Older adults with cognitive impairment
In 10 trials with 516 people, melatonin added about 12 minutes of total sleep and 1.8 MMSE points; the authors judged the gains modest and short of definitive.
Sleep in cancer
Pooling 7 trials in people with cancer, melatonin had no significant overall effect on sleep quality, with very high heterogeneity between studies.
Musculoskeletal pain
A meta-analysis found modest pain benefits in chronic musculoskeletal pain, mostly below clinically important thresholds, with limited evidence after surgery.
Cardiometabolic markers
A dose-response meta-analysis found small reductions in systolic blood pressure, fasting glucose, LDL cholesterol and inflammatory markers with melatonin supplements.
Dosing Data
A dietary supplement in the US and a prescription medicine (prolonged-release 2 mg) for insomnia over 55 in the EU and UK. Trial doses range from 2 to 10 mg at night.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above; the US supplement form carries no label of this kind.
Contraindications & Cautions
The prescription product has a label; the supplement does not.
Legal Status
Melatonin's status depends entirely on where you are.
Frequently Asked Questions
?Is melatonin a sleeping pill?
No. It signals darkness to the body clock rather than sedating, so its effects are modest.
?What dose do the trials use?
The licensed prolonged-release product is 2 mg two hours before bed; children's trials used 3 mg.
?Why is it a supplement in the US and a drug in Europe?
US law treats it as a dietary supplement; Europe licenses a prolonged-release product as a medicine for insomnia from age 55.
?Does what is in the bottle match the label?
In the US there is no requirement that it does, and testing has repeatedly found doses well away from what is printed.
?Does melatonin prevent delirium?
After surgery in older adults, pooled trials found less delirium (21.0% against 28.4%). In older medical inpatients, a trial was stopped early for futility.
?Does melatonin help migraine?
A meta-analysis of 9 trials found fewer headache days and shorter, milder attacks than placebo, though it was generally less effective than amitriptyline.
References
- [pubmed] Wade AG, et al. "Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes." Curr Med Res Opin, 2007;23(10):2597-605. PMID: 17875243.
- [pubmed] Wade AG, et al. "Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety." BMC Med, 2010;8:51. PMID: 20712869.
- [pubmed] Jalilolghadr S, et al. "The effect of treatment with melatonin on primary school aged children with difficulty in initiation and maintenance of sleep." Turk J Pediatr, 2022;64(6):993-1000. PMID: 36583881.
- [pubmed] Lemoine P, et al. "Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects." J Sleep Res, 2007;16(4):372-80. PMID: 18036082.
- [pubmed] Liu J, et al. "MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective." Annu Rev Pharmacol Toxicol, 2016;56:361-83. PMID: 26514204.
- [pubmed] Comai S, et al. "Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views." J Pineal Res, 2024;76(7):e13011. PMID: 39400423.
- [pubmed] Mun JG, et al. "A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults." J Diet Suppl, 2024;21(2):182-194. PMID: 37150895.
- [other] EMA register: Circadin, authorised June 29, 2007.
- [clinical-trial] Qian J, et al. "Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant." Diabetes Care, 2026;49(8):1498-1506. PMID: 42346809.
- [pubmed] Borges JMMF, et al. "Melatonin or ramelteon for the prevention of postoperative delirium in elderly patients: A systematic review and meta-analysis of randomized clinical trials." J Clin Anesth, 2026;110:112151. PMID: 41702325.
- [pubmed] Al Alawi AM, et al. "Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE)." BMJ Open, 2026;16(1):e107775. PMID: 41592826.
- [pubmed] Abouelmagd ME, et al. "Efficacy and Safety of Melatonin in Migraine Prophylaxis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Curr Pain Headache Rep, 2026;30(1):25. PMID: 41627537.
- [pubmed] Mdluli NT, et al. "Melatonin for sleep and cognitive outcomes in older adults with cognitive impairment: a meta-analysis of randomised controlled trials." Age Ageing, 2025;54(11). PMID: 41240058.
- [pubmed] Abbasi MM, et al. "Safety and Efficacy of Melatonin for Sleep Disorders in Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials." Curr Rev Clin Exp Pharmacol, 2026. PMID: 42708337.
- [pubmed] K GP, et al. "Oral Melatonin Supplementation for Sleep Disturbances in Children with Cerebral Palsy: A Randomized Double-Blind Controlled Trial." Indian J Pediatr, 2026;93(3):259-264. PMID: 41369870.
- [pubmed] Wu K, et al. "Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials." Pain, 2026;167(9):2014-2025. PMID: 42378431.
- [pubmed] Mohammadi S, et al. "Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis." Nutrients, 2025;18(1). PMID: 41515249.
- [pubmed] Bejarano I, et al. "Hepatic Safety of Adjunctive High-Dose Melatonin in Participants Receiving Ocrelizumab for Primary Progressive Multiple Sclerosis: Liver Toxicity Findings from a Phase I/II Randomised Clinical Trial (MELATOMS-1)." CNS Drugs, 2026;40(4):579-596. PMID: 41706381.
- [pubmed] Young TA, et al. "A cost-effectiveness analysis of melatonin in comparison with midazolam for anxiety prior to general anaesthesia in children: the MAGIC randomised controlled trial (melatonin for anxiety prior to general anaesthesia in children)." BMC Anesthesiol, 2025;26(1):47. PMID: 41408524.
Sources & Citations
Studies were read from their PubMed abstracts. Read October 7, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.