Herb & supplement monograph

Melatonin Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by ·Updated July 2026
What is this page for?

First and foremost: how Melatonin interacts with medications. The heart of this page is the interaction list — every drug Melatonin is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Melatonin is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

Check Melatonin against your medication

Add one medication
Melatonin
+
Start typing any prescription or over-the-counter drug name.
Reviewed by licensed pharmacists Sourced from Natural Medicines
On this page

Melatonin Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Melatonin drug interaction appears low for most people. None of the listed interactions are rated major, and although many are graded moderate, nearly all rest on theoretical reasoning or limited human reports rather than proven harm.

Interactions deserving the most attention

The best-documented concern involves extended-release nifedipine, since melatonin blunted this blood pressure medicine's effect in human studies. Fluvoxamine can sharply raise melatonin levels, which may strengthen its effects, including sedation. There are also case reports of altered clotting measures with warfarin, and some evidence that melatonin may increase seizure frequency in certain patients, especially children with neurological impairment. Because bleeding risk, blood pressure, blood sugar, and seizure control leave little room for error, these combinations deserve the closest watching.

What the rest of the list means

Melatonin appears alongside a very long list of medications, but that number mostly reflects broad drug categories, not proven problems with each one. Many entries are theoretical, based on how melatonin might affect liver enzymes the body uses to clear certain medications. Several predicted effects, such as those with methamphetamine, have only been seen in animal or lab research and have not been shown in people.

Check your medications against Melatonin

Based on HelloPharmacist’s Melatonin interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Melatonin

1461 medications have a known interaction with Melatonin, graded by severity. Select any drug for the full evidence-based detail.

2,830 drugs
6-mercaptopurinePurinethol
Moderate Immunosuppressants

Theoretically, melatonin might interfere with immunosuppressive therapy.

Read the full Melatonin + 6-mercaptopurine interaction 6-mercaptopurine drug page: uses, dosage & side effects
AbciximabReoPro
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Melatonin + Abciximab interaction
AbrocitinibCibinqo
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Melatonin + Abrocitinib interaction Abrocitinib drug page: uses, dosage & side effects
AcarboseGlucobay, Prandase, Precose
Moderate Antidiabetes Drugs

Theoretically, taking melatonin with antidiabetes drugs might increase the risk of hypoglycemia.

Read the full Melatonin + Acarbose interaction Acarbose drug page: uses, dosage & side effects
AcebutololRhotral, Sectral
Moderate Antihypertensive Drugs

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.

Read the full Melatonin + Acebutolol interaction Acebutolol drug page: uses, dosage & side effects
AcenocoumarolSintrom
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Melatonin + Acenocoumarol interaction
AcepromazineAtravet
Moderate Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

Read the full Melatonin + Acepromazine interaction
AcetaminophenChildren's Tylenol, Children's Tylenol Meltaways, Tylenol, Tylenol Ex Strength
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen interaction Acetaminophen drug page: uses, dosage & side effects
Acetaminophen, AspirinGemnisyn
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Aspirin interaction
Acetaminophen, Aspirin, CaffeineExcedrin, Excedrin Extra Strength, Excedrin Migraine
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Melatonin + Acetaminophen, Aspirin, Caffeine interaction
Acetaminophen, Brompheniramine, PhenylpropanolamineDimetapp Cold and Flu
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Brompheniramine, Phenylpropanolamine interaction
Acetaminophen, ButalbitalAxocet, Bancap, Bucet, Butex Forte, Esgic CF, Orbivan CF +5 more
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Butalbital interaction
Acetaminophen, Butalbital, CaffeineEsgic, Esgic Plus, Fiogesic, Fioricet, Repan, Tecnal +1 more
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Butalbital, Caffeine interaction Acetaminophen, Butalbital, Caffeine drug page: uses, dosage & side effects
Acetaminophen, Butalbital, Caffeine, CodeineEsgic with Codeine, Fioricet w/ Codeine
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Butalbital, Caffeine, Codeine interaction
Acetaminophen, Butalbital, CodeineBancap w/ Codeine
Moderate Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

Read the full Melatonin + Acetaminophen, Butalbital, Codeine interaction
Acetaminophen, Butalbital, Codeine PhosphatePhrenilin #3
Moderate Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

Read the full Melatonin + Acetaminophen, Butalbital, Codeine Phosphate interaction
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, PhenylephrineHycomine Compound
Moderate Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

Read the full Melatonin + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction
Acetaminophen, Caffeine, CodeineGesic C15, Gesic C30, Gesic C8, Lenoltec 1, Lenoltec 2, Lenoltec 3 +1 more
Moderate Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.

Read the full Melatonin + Acetaminophen, Caffeine, Codeine interaction
Acetaminophen, Caffeine, Codeine, SalicylamideCodalan No.1, Codalan No.2, Codalan No.3
Moderate Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.

Read the full Melatonin + Acetaminophen, Caffeine, Codeine, Salicylamide interaction
Acetaminophen, Caffeine, DihydrocodeineDHC Plus, Panlor DC, Panlor SS
Moderate Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.

Read the full Melatonin + Acetaminophen, Caffeine, Dihydrocodeine interaction
Acetaminophen, Caffeine, IsomethepteneMigralam
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Caffeine, Isometheptene interaction
Acetaminophen, Caffeine, PyrilamineMidol Max Strength Menstrual
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Caffeine, Pyrilamine interaction
Acetaminophen, Chlorpheniramine Maleate, Dextromethorphan HbrVicks Formula 44M Cough, Cold & Flu Relief
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Chlorpheniramine Maleate, Dextromethorphan Hbr interaction
Acetaminophen, Chlorpheniramine, Codeine, PhenylephrineColrex
Moderate Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction
Acetaminophen, Chlorpheniramine, DextromethorphanCoricidin II Extra Strength Cold and Flu
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Dextromethorphan interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan HydrobromideCoricidin HBP Maximum Strength Flu
Moderate Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Dextromethorphan Hydrobromide interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PhenylpropanolamineMulti Symptom Cold Relief
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PseudoephedrineChildren's Tylenol Cold Plus Cough, Tylenol Cold Ex Strength
Moderate Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction
Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, SalicylamideRhinogesic GG
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, Salicylamide interaction
Acetaminophen, Chlorpheniramine, PhenylephrineAlka-Seltzer PLUS, Histex SR, Protid
Moderate Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.

Read the full Melatonin + Acetaminophen, Chlorpheniramine, Phenylephrine interaction
Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

  • Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
  • Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
  • Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
  • No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

  • Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
  • Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
  • Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

  • Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
  • Each drug listed above links to the full report for that exact Melatonin combination — clinical detail, likelihood, evidence level, and citations.
  • Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
The big picture

The kinds of drugs Melatonin affects

Every type of medication (drug category) Melatonin is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 18 drug categories Melatonin interacts with
Anticoagulant/antiplatelet DrugsAnticonvulsantsAntidiabetes DrugsAntihypertensive DrugsCaffeineCns DepressantsContraceptive DrugsCytochrome P450 1a2 (cyp1a2) SubstratesCytochrome P450 2c19 (cyp2c19) SubstratesFluvoxamine (luvox)ImmunosuppressantsMethamphetamine (desoxyn)Nifedipine Gits (procardia Xl)Seizure Threshold Lowering DrugsWarfarin (coumadin)Cytochrome P450 2d6 (cyp2d6) SubstratesCytochrome P450 3a4 (cyp3a4) SubstratesFlumazenil (romazicon)
Anticoagulant/Antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.

Likelihood Possible Evidence B
Anticonvulsants

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking melatonin with antidiabetes drugs might increase the risk of hypoglycemia.
Some clinical research shows that melatonin reduces levels of fasting blood glucose and improves glycemic control. However, other research suggests that melatonin might impair glucose utilization and increase insulin resistance, while other research has found no effect on glucose levels. Until more is known, use melatonin cautiously in combination with antidiabetes drugs.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.
Some clinical research suggests that taking melatonin decreases blood pressure in healthy adults. Also, melatonin seems to lower systolic and diastolic blood pressure in individuals with high blood pressure at nighttime or untreated essential hypertension. However, melatonin seems to worsen blood pressure in patients who are taking antihypertensive medications. Immediate-release melatonin 5 mg at night in combination with nifedipine GITS (Procardia XL) increases systolic blood pressure an average of 6.5 mmHg, diastolic blood pressure by an average of 4.9 mmHg, and heart rate by 3.9 bpm. Also, results from animal research suggest that melatonin reduces the effectiveness of certain antihypertensive drugs, including methoxamine and clonidine.

Likelihood Possible Evidence A
Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.
Some evidence suggests that caffeine consumption can decrease endogenous melatonin levels, while other evidence suggests that caffeine increases endogenous melatonin levels. When administered in combination with melatonin supplements, caffeine seems to increase melatonin effects and levels. The reason for this discrepancy is not completely clear. Part of the discrepancy may result from the fact that caffeine can inhibit melatonin synthesis as well as inhibit melatonin metabolism. By functioning as an adenosine receptor antagonist, caffeine may indirectly inhibit the synthesis of melatonin. Conversely, because melatonin and caffeine are both metabolized by cytochrome P450 1A2 (CYP1A2) enzyme, concomitant use of melatonin and caffeine may reduce the metabolism of melatonin, resulting in higher serum levels.

Likelihood Probable Evidence B
Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.
Contraceptive drugs can increase the levels of endogenous melatonin. Theoretically, these drugs may increase the effects and adverse effects of oral melatonin.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, taking fluvoxamine with melatonin might increase levels of melatonin.
Fluvoxamine can significantly increase melatonin levels. In some cases, fluvoxamine might increase bioavailability of exogenously administered melatonin by up to 20 times. Some researchers think this might be a beneficial interaction and be potentially useful for cases of refractory insomnia. However, this interaction might also cause unwanted excessive drowsiness and possibly other adverse effects. Fluvoxamine is known to increase endogenous melatonin secretion. It seems to increase serum levels of exogenously administered melatonin possibly by decreasing melatonin metabolism by inhibiting cytochrome P450 (CYP450) 1A2 and 2C19 or by inhibiting melatonin elimination. This effect has been found in healthy people taking fluvoxamine 50-75 mg and melatonin 5 mg.

Likelihood Probable Evidence B
Immunosuppressants

Theoretically, melatonin might interfere with immunosuppressive therapy.
Melatonin can stimulate immune function. Theoretically, melatonin might interfere with immunosuppressive therapy.

Likelihood Possible Evidence B
Methamphetamine (Desoxyn)

Theoretically, taking melatonin with methamphetamine may increase the adverse effects of methamphetamine.
Animal research suggests that melatonin exacerbates the adverse effects of methamphetamine, resulting in greater depression of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activity, as well as a significant reduction in dopamine levels. This has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine Gits (Procardia Xl)

Theoretically, taking melatonin with extended release nifedipine reduces the effects of nifedipine.
Melatonin can decrease the effectiveness of extended release nifedipine (GITS). Immediate-release melatonin 5 mg at night in combination with nifedipine GITS 30-60 mg daily increases systolic and blood pressure by an average of 6.5 mmHg and 4.9 mmHg, respectively. Concomitant use with melatonin also increases heart rate by 3.9 bpm. The mechanism of this interaction is not known.

Likelihood Probable Evidence B
Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2D6.
Laboratory research suggests that certain lots of melatonin inhibit CYP2D6. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2D6 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence D
Flumazenil (Romazicon)

Theoretically, taking flumazenil with melatonin might reduce the effects of melatonin.
Animal research shows that flumazenil may inhibit the effect of melatonin.

Likelihood Possible Evidence D
Monograph

Melatonin: Uses, Safety & Side Effects

Medically reviewed by · Reviewed July 2026 ·
The bottom line

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is strongest for certain circadian (body-clock) disorders and is more mixed for everyday insomnia. It is generally well tolerated for short-term use, but talk with your pharmacist or doctor before starting, especially for children or during pregnancy.

Melatonin
Part used
Hormone naturally made by the pineal gland; supplements are usually made synthetically
Common forms
Tablets, capsules, gummies, sublingual (under-the-tongue) tablets, liquids, extended-release tablets
People commonly use it for
  • Trouble falling asleep (insomnia)
  • Jet lag
  • Delayed sleep phase syndrome
  • Non-24-hour sleep-wake disorder
  • Shift-work sleep problems
  • Sleep problems in some children with conditions like autism or ADHD

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance
OverallUse caution

Generally well tolerated for short-term use, but long-term safety is less certain and product quality varies.

PregnancyPossibly Unsafe

When used orally or parenterally in high doses or with frequent use. High doses of melatonin 75-300 mg daily seem to inhibit ovulation, causing a cont...

Read the full pregnancy detail
BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Jump to a section

Overview

Melatonin is a hormone your body makes on its own, mainly in a small part of the brain called the pineal gland. Its job is to help control your body's internal clock, also called the circadian rhythm. Levels normally rise in the evening when it gets dark and fall in the morning, which helps signal when it is time to sleep and time to wake.

As a supplement, melatonin is usually made synthetically in a lab rather than taken from an animal source. It is sold over the counter in many countries and is one of the most popular sleep aids. People take it most often for jet lag, for trouble falling asleep, and for sleep problems linked to a body clock that is out of sync.

How it works

Melatonin works mainly by acting on melatonin receptors in the brain that are part of the body's master clock. By sending an "it's nighttime" signal, it can help shift the timing of sleep and tell the body it is time to wind down. This is why it is often more useful for fixing the timing of sleep than for acting as a strong sedative.

Because it is a natural hormone, taking it at the right time of day matters. Taken in the evening it can help move sleep earlier, while taken at the wrong time it could shift the clock in an unwanted direction. Researchers are still studying its other possible effects, such as antioxidant activity, and much of that work is early or based on laboratory studies.

Effectiveness

Does Melatonin work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by .

Evidence overview · 94 uses evaluated
2 Likely effective 9 Possibly effective 10 Leans ineffective 73 Insufficient evidence
How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.
2Likely EffectiveGood evidence, though not yet conclusive.
3Possibly EffectiveSome evidence suggests a benefit.
4Possibly IneffectiveSome evidence it may not help.
5Likely IneffectiveFairly strong evidence it doesn’t help.
6IneffectiveStrong evidence it doesn’t work.
7Insufficient Reliable Evidence to RateToo little research to say either way.
Likely Effective Delayed sleep phase syndrome (DSPS)
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin shortens the time needed to fall asleep in children and adults with DSPS.

Likely Effective Non-24-hour sleep wake disorder
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin improves non-24-hour sleep wake disorder in blind children and adults.

Possibly Effective Beta blocker-induced insomnia
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin seems to improve sleep in patients with insomnia related to the use of beta-blockers.

Possibly Effective Emergence delirium
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin seems to be beneficial for reducing sevoflurane-induced agitation in children. It is unclear if oral melatonin is beneficial for adults undergoing surgery.

Possibly Effective Hypertension
Rating & evidence shown verbatim from Natural Medicines

Oral controlled-release melatonin seems to reduce blood pressure by a small amount in patients with hypertension. Immediate-release melatonin may not have the same effect.

Possibly Effective Jet lag
Rating & evidence shown verbatim from Natural Medicines

Taking oral melatonin 2-3 mg daily while travelling seems to improve alertness and reduce daytime sleepiness in people with jet lag. It is unclear if it improves sleep efficiency in this population. Higher doses might have a hypnotic effect.

Possibly Effective Pre-procedural anxiety
Rating & evidence shown verbatim from Natural Medicines

Most research shows that oral or sublingual melatonin reduces preoperative anxiety in adults. The benefit in children is unclear.

Possibly Effective Pre-procedural sedation
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin might reduce the sedative dose required to achieve adequate sedation in children. It is unclear if oral melatonin is beneficial for this purpose in adults.

Possibly Effective Sunburn
Rating & evidence shown verbatim from Natural Medicines

Most research shows that topical melatonin seems to protect against erythema from ultraviolet (UV) light exposure.

Possibly Effective Temporomandibular disorders (TMD)
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin seems to moderately reduce pain in females with TMD.

Possibly Effective Thrombocytopenia
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin seems to improve and prevent thrombocytopenia associated with cancer, cancer treatment, and other disorders.

Possibly Ineffective Athletic performance
Rating & evidence shown verbatim from Natural Medicines

Most research suggests that oral melatonin does not improve athletic performance or physical strength.

Possibly Ineffective Cachexia
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to improve appetite or body composition in patients with cachexia and cancer.

Possibly Ineffective Cancer-related fatigue
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to improve fatigue in patients with cancer.

Possibly Ineffective Cancer-related pain
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to improve pain in patients with cancer.

Possibly Ineffective Critical illness (trauma)
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to be beneficial for reducing hospital stay in critically ill patients.

Possibly Ineffective Dementia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin improves behavior or cognition in patients with dementia. However, it might reduce evening confusion (sundowning).

Possibly Ineffective Infertility
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to increase fertility in females undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Possibly Ineffective Shift work disorder
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not seem to improve sleep in individuals doing shift work.

Likely Ineffective Benzodiazepine withdrawal
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin does not facilitate benzodiazepine discontinuation in patients with insomnia.

Likely Ineffective Depression
Rating & evidence shown verbatim from Natural Medicines

Most research shows that oral melatonin does not reduce symptoms of depression or prevent depression. In some patients, taking melatonin might make symptoms worse.

Also studied for 73 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Acute kidney injury (AKI)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for acute kidney injury.

Insufficient Reliable Evidence To Rate Age-related macular degeneration (AMD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin prevents vision loss in patients with AMD.

Insufficient Reliable Evidence To Rate Atopic dermatitis (eczema)
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin might improve some symptoms of atopic dermatitis. However, it is unclear if it improves sleep in this population.

Insufficient Reliable Evidence To Rate Attention deficit-hyperactivity disorder (ADHD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for ADHD.

Insufficient Reliable Evidence To Rate Autism spectrum disorder
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Benign prostatic hyperplasia (BPH)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for BPH.

Insufficient Reliable Evidence To Rate Bipolar disorder
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Bronchopulmonary dysplasia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin reduces the risk of bronchopulmonary dysplasia (BPD) in premature infants.

Insufficient Reliable Evidence To Rate Chronic fatigue syndrome (CFS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for patients with CFS.

Insufficient Reliable Evidence To Rate Chronic obstructive pulmonary disease (COPD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for COPD.

Insufficient Reliable Evidence To Rate Cognitive impairment
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Colorectal cancer
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for colorectal cancer prevention.

Insufficient Reliable Evidence To Rate Contraception
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral melatonin for contraception, there is insufficient reliable information about the clinical effects of melatonin for this use.

Insufficient Reliable Evidence To Rate Coronary artery bypass graft (CABG) surgery
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for recovery from CABG surgery.

Insufficient Reliable Evidence To Rate Coronavirus disease 2019 (COVID-19)
Rating & evidence shown verbatim from Natural Medicines

Preliminary clinical studies suggest that oral melatonin may reduce disease severity in patients with COVID-19, although some conflicting findings exist.

Insufficient Reliable Evidence To Rate Delirium
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for preventing delirium in hospitalized patients; the available research is conflicting.

Insufficient Reliable Evidence To Rate Diabetes
Rating & evidence shown verbatim from Natural Medicines

Most research shows that oral melatonin is beneficial for improving glycemic control. However, it is unclear if oral melatonin is beneficial in patients with type 2 diabetes.

Insufficient Reliable Evidence To Rate Diabetic neuropathy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving pain in patients with diabetic neuropathy.

Insufficient Reliable Evidence To Rate Dry mouth
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for dry mouth caused by radiation treatment.

Insufficient Reliable Evidence To Rate Dysmenorrhea
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for dysmenorrhea.

Insufficient Reliable Evidence To Rate Endometriosis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin reduces endometriosis-related pain.

Insufficient Reliable Evidence To Rate Endotracheal intubation-associated adverse effects
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for endotracheal intubation-related hemodynamic effects.

Insufficient Reliable Evidence To Rate Epilepsy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for epilepsy in children or adults.

Insufficient Reliable Evidence To Rate Fibromyalgia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Gastroesophageal reflux disease (GERD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for GERD.

Insufficient Reliable Evidence To Rate Heart failure
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for heart failure.

Insufficient Reliable Evidence To Rate Helicobacter pylori
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for Helicobacter pylori eradication.

Insufficient Reliable Evidence To Rate Irritable bowel syndrome (IBS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for IBS.

Insufficient Reliable Evidence To Rate Ischemia-reperfusion injury
Rating & evidence shown verbatim from Natural Medicines

It is unclear if intravenous or intracoronary melatonin is beneficial for ischemia-reperfusion injury.

Insufficient Reliable Evidence To Rate Kidney failure
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving mood and quality of life in patients on hemodialysis.

Insufficient Reliable Evidence To Rate Kidney transplant
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving post-transplant kidney function.

Insufficient Reliable Evidence To Rate Lung cancer
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial in patients with early stage non-small cell lung cancer (NSCLC).

Insufficient Reliable Evidence To Rate Melasma
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral melatonin for melasma and other causes of hyperpigmentation, there is insufficient reliable information about the clinical effects of melatonin for these conditions.

Insufficient Reliable Evidence To Rate Menopausal symptoms
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving symptoms of menopause; evidence is conflicting.

Insufficient Reliable Evidence To Rate Metabolic syndrome
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Multiple sclerosis (MS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for MS.

Insufficient Reliable Evidence To Rate Myocardial infarction (MI)
Rating & evidence shown verbatim from Natural Medicines

The benefits of administering oral or intravenous melatonin immediately after an MI are unclear.

Insufficient Reliable Evidence To Rate Neonatal encephalopathy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral or intravenous melatonin is beneficial for neonates with encephalopathy.

Insufficient Reliable Evidence To Rate Nocturnal enuresis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for reducing nighttime wettings.

Insufficient Reliable Evidence To Rate Nonalcoholic fatty liver disease (NAFLD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for NAFLD.

Insufficient Reliable Evidence To Rate Obesity
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for improving weight loss.

Insufficient Reliable Evidence To Rate Oral mucositis
Rating & evidence shown verbatim from Natural Medicines

Most research shows that melatonin does not prevent or reduce the severity of oral mucositis in patients with head and neck cancer receiving radiation and chemotherapy. It is unclear if oral or topical melatonin is beneficial in patients with other types of cancer.

Insufficient Reliable Evidence To Rate Osteopenia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving bone mineral density.

Insufficient Reliable Evidence To Rate Osteoporosis
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral melatonin for osteoporosis, there is insufficient reliable information about the clinical effects of melatonin for this condition.

Insufficient Reliable Evidence To Rate Pain (chronic)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for most causes of chronic pain.

Insufficient Reliable Evidence To Rate Periodontitis
Rating & evidence shown verbatim from Natural Medicines

Small clinical studies suggest that oral melatonin may improve some measures of periodontitis severity.

Insufficient Reliable Evidence To Rate Polycystic ovary syndrome (PCOS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for PCOS.

Insufficient Reliable Evidence To Rate Postoperative nausea and vomiting (PONV)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for reducing PONV.

Insufficient Reliable Evidence To Rate Postoperative pain
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for reducing pain postoperatively.

Insufficient Reliable Evidence To Rate Postoperative recovery
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin improves the rate of recovery after surgery.

Insufficient Reliable Evidence To Rate Postoperative sleep disturbance
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for improving postoperative sleep disturbance.

Insufficient Reliable Evidence To Rate Postural tachycardia syndrome (POTS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if melatonin is beneficial for POTS.

Insufficient Reliable Evidence To Rate Pre-eclampsia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin reduces the severity of pre-eclampsia.

Insufficient Reliable Evidence To Rate Premenstrual syndrome (PMS)
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Prostate cancer
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin has only been evaluated in combination with medication; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Pruritus
Rating & evidence shown verbatim from Natural Medicines

Small clinical trials suggest that oral melatonin might be beneficial for some types of pruritus.

Insufficient Reliable Evidence To Rate Psoriasis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if topical melatonin is beneficial for psoriasis.

Insufficient Reliable Evidence To Rate Radiation dermatitis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if topical melatonin is beneficial for radiation-related dermatitis.

Insufficient Reliable Evidence To Rate Rapid eye movement sleep behavior disorder (RBD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for RBD.

Insufficient Reliable Evidence To Rate Restless legs syndrome (RLS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for RLS.

Insufficient Reliable Evidence To Rate Rheumatoid arthritis (RA)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for RA.

Insufficient Reliable Evidence To Rate Sarcoidosis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Schizophrenia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for schizophrenia or for attenuating the adverse effects associated with antipsychotic medications.

Insufficient Reliable Evidence To Rate Seasonal affective disorder (SAD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for SAD.

Insufficient Reliable Evidence To Rate Sepsis
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for sepsis in neonates or adults.

Insufficient Reliable Evidence To Rate Smoking cessation
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial in patients trying to quit smoking.

Insufficient Reliable Evidence To Rate Stabbing headache
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral melatonin for stabbing headaches, there is insufficient reliable information about the clinical effects of melatonin for this condition.

Insufficient Reliable Evidence To Rate Stress
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for stress reduction.

Insufficient Reliable Evidence To Rate Tardive dyskinesia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for this condition.

Insufficient Reliable Evidence To Rate Tension headache
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for reducing the frequency of tension headaches.

Insufficient Reliable Evidence To Rate Tinnitus
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for improving tinnitus intensity or severity.

Insufficient Reliable Evidence To Rate Traumatic brain injury (TBI)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral melatonin is beneficial for children who have experienced a concussion.

Insufficient Reliable Evidence To Rate Ulcerative colitis
Rating & evidence shown verbatim from Natural Medicines

Oral melatonin may be modestly beneficial for reducing symptoms or sustaining remission in patients using the medication mesalazine.

Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.

Safety & precautions

For most healthy adults, melatonin appears to be reasonably safe for short-term use. Long-term safety is less well studied, so it is not clear how safe it is to take every night for months or years. Because it is a hormone, some experts have raised questions about effects on hormones and development, especially in children.

Talk with a healthcare provider before giving melatonin to a child or teen, and before using it if you have a seizure disorder, an autoimmune condition, depression, or other ongoing health problems. Keep in mind that supplement quality is not tightly regulated, and the actual amount of melatonin in a product can differ from what the label says. Look for products with third-party testing when possible.

For pregnancy and breastfeeding, there is not enough reliable information to call it safe, so it is best to avoid melatonin during these times unless your doctor specifically recommends it. Melatonin can also cause drowsiness, so do not drive or use machinery until you know how it affects you.

Side effects

Melatonin is usually well tolerated, but some people have side effects. The most common include daytime drowsiness or grogginess, headache, dizziness, and nausea. Some people report vivid dreams or feeling more irritable.

Less common effects can include mild mood changes or a feeling of being "foggy" the next morning, especially with higher doses or extended-release forms. Serious side effects are rare. Stop using it and contact a healthcare provider if you have an unusual or severe reaction.

Melatonin: Reported Adverse Effects

Documented safety reports on Melatonin from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.

Orally, melatonin is generally well tolerated.

Most Common Adverse Effects:

Orally: Dizziness, drowsiness, headache, and nausea.

Serious Adverse Effects (Rare):

Orally: There is concern that melatonin may increase the risk for seizure.

Reports by condition
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) Endocrine

Orally, melatonin use might be associated with higher rates of precocious puberty, growth hormone deficiency, elevated cortisol, and increased progesterone. A case of gynecomastia (increased breast size) has been reported for a 56 year-old patient with amyotrophic lateral sclerosis (ALS) who used oral melatonin, long-term. Also, reduced sperm concentration and sperm motility has been reported for two men who used oral melatonin 3 mg daily for 6 months. Improvement in sperm quality was observed for only one of the two men following melatonin cessation.

  1. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  2. De Bleecker JL, Lamont BH, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology. 1999 Jul 22;53(2):435-6.
  3. Luboshitzky, R., Shen-Orr, Z., Nave, R., Lavi, S., and Lavie, P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23(4):572-578.
Attention deficit-hyperactivity disorder (ADHD) Psychiatric

Orally, melatonin may cause mood changes, including dysphoria (sadness), dips in mood, nervousness, suicide or self-injury, or transient depression. Delusions and hallucinations have also been reported in clinical research. An analysis of adverse event case reports indicates that drug abuse, dependence, and withdrawal have been associated with melatonin use; however, the rate appears to be lower when compared with all other medications combined or sleep medications.

This analysis also suggests that melatonin use might be associated with educational problems, social behavior disturbances, defiant behavior, oppositional defiant disorder, and school refusal at disproportionately higher rates when compared with all other drugs combined or other sleep medications. An isolated incident of aggressiveness was also noted in a child diagnosed with attention deficit-hyperactivity disorder (ADHD) who took melatonin in combination with methylphenidate. Severe irritability has been reported in two children with autism spectrum disorder who had abruptly discontinued melatonin due to the completion of a clinical trial.

  1. Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186.
  2. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi
  3. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  4. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614.
  5. Alstadhaug, K. B., Odeh, F., Salvesen, R., and Bekkelund, S. I. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 10-26-2010;75(17):1527-1532.
  6. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  7. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30.
  8. Boeve, B. F., Silber, M. H., and Ferman, T. J. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281-284.
  9. Tjon Pian Gi CV, Broeren JP, Starreveld JS, A Versteegh FG. Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study. Eur J Pediatr 2003;162:554-5.
  10. Hayashi M, Mishima K, Fukumizu M, et al. Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: A randomized controlled trial. J Autism Dev Disord 2021.
Back pain Musculoskeletal

Orally, melatonin might increase fall risk. Analysis of a large adverse event database suggests that the rate of accidents and falls is higher with melatonin use when compared with the average rate of all other medications combined. However, the rate of accidents and falls with melatonin use seems to be lower when compared with other sleep medications. Other clinical evidence shows that a single dose of melatonin 3 mg may increase fall risk due to increased postural swaying while standing on one or both feet in healthy adults ages 60-71 years.

A single case of ataxia has been reported for an 81-year-old female who used melatonin for 4 days. Weakened muscle power has been reported for two patients treated with melatonin 5 mg in the evening. Some melatonin preparations contain contaminants that are associated with eosinophilia-myalgia syndrome. There are also reports of back pain, dropped head syndrome, fractures, growth retardation, and myalgia associated with melatonin intake.

  1. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  2. Lui MFG, Chow HKD, Wong WMK, Tsang WNW. Melatonin affects postural control in community-dwelling older adults while dual-tasking: a randomized observation study. J Aging Phys Act. 2018 May 29:1-24.
  3. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520.
  4. Klupinska, G., Poplawski, T., Drzewoski, J., Harasiuk, A., Reiter, R. J., Blasiak, J., and Chojnacki, J. Therapeutic effect of melatonin in patients with functional dyspepsia. J.Clin.Gastroenterol. 2007;41(3):270-274.
  5. Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5.
  6. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res To
Cluster headache Neurologic/CNS

Orally, melatonin may cause migraine-like headache or dizziness. Often these symptoms occur during the first few days of treatment and subside after a few days. Melatonin may also cause drowsiness or fatigue when taken orally. These symptoms appear to be more common if melatonin is taken in the morning or at very high doses (greater than 50 mg). A case of excessive drowsiness has been reported when melatonin was combined with citalopram, nortriptyline, and oxycodone. Sedation improved with discontinuation of melatonin. Indiscriminate use of melatonin may cause irregular sleep-wake cycles to occur. Less commonly, melatonin may also cause behavior worsening, confusion or disorientation, nighttime awakening, mood swings or agitation, stereotypy, tic, excitement before bedtime, insomnia, nightmares or more intense dreams, feelings of a "rocking" sensation, or reduced alertness when taken orally.

A case of generalized epilepsy has reportedly occurred after treatment with melatonin for 4 months. Also, some case reports raise concerns about increased risk of seizure with melatonin treatment, but conflicting evidence suggests that melatonin may decrease the risk of seizures. One patient experienced hyponatremia with confusion and seizures after taking prolonged-release melatonin 2 mg. However, malnutrition and cannabis abuse were also thought to contribute to this reaction.

Although there is concern that melatonin might affect cognitive function in healthy adults, research in humans suggests that oral or topical melatonin do not impact most measures of cognitive function.

  1. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5.
  2. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30.
  3. Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006;45:512-9.
  4. Buscemi, N., Vandermeer, B., Pandya, R., Hooton, N., Tjosvold, L., Hartling, L., Baker, G., Vohra, S., and Klassen, T. Melatonin for treatment of sleep disorders. Evid.Rep.Technol.Assess.(Summ.) 2004;(108):1-7.
  5. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  6. Bendz, L. M. and Scates, A. C. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann.Pharmacother. 2010;44(1):185-191.
  7. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254.
  8. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387.
  9. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614.
  10. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89.
  11. Eckerberg B, Lowden A, Nagai R, Akerstedt T. Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study. Chronobiol Int. 2012;29(9):1239-48.
  12. Khezri MB, Merate H. The effects of melatonin on anxiety and pain scores of patients, intraocular pressure, and operating conditions during cataract surgery under topical anesthesia. Indian J Ophthalmol. 2013;61(7):319-24.
  13. Khezri MB, Oladi MR, Atlasbaf A. Effect of melatonin and gabapentin on anxiety and pain associated with retrobulbar eye block for cataract surgery: a randomized double-blind study. Indian J Pharmacol. 2013;45(6):581-6.
  14. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2017;56(11):948-57.e4.
  15. Esmaeili A, Nassiri Toosi M, Taher M, et al. A pilot randomized, clinical trial of the anti-pruritus effect of melatonin in patients with chronic liver disease. Iran J Pharm Res 2021;20(2):462-472.
  16. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  17. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi
  18. Klupinska, G., Poplawski, T., Drzewoski, J., Harasiuk, A., Reiter, R. J., Blasiak, J., and Chojnacki, J. Therapeutic effect of melatonin in patients with functional dyspepsia. J.Clin.Gastroenterol. 2007;41(3):270-274.
  19. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391.
  20. Alstadhaug, K. B., Odeh, F., Salvesen, R., and Bekkelund, S. I. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 10-26-2010;75(17):1527-1532.
  21. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792.
  22. Chojnacki C, Walecka-Kapica E, Lokiec K, et al. Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women. Endokrynol Pol. 2013;64(2):114-20.
  23. Ameri A, Frouz Asadi M, Ziaei A, et al. Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial. Inflammopharmacology 2023;31(1):265-274.
  24. Suhner A, Schlagenhauf P, Johnson R, et al. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998;15:655-66.
  25. Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32.
  26. Onseng K, Johns NP, Khuayjarernpanishk T, et al. Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation. J Altern Complement Med 2017;23(12):957-63.
  27. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32.
  28. Fallah R, Shoroki FF, Ferdosian F. Safety and efficacy of melatonin in pediatric migraine prophylaxis. Curr Drug Saf. 2015;10(2):132-5.
  29. Hayashi M, Mishima K, Fukumizu M, et al. Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: A randomized controlled trial. J Autism Dev Disord 2021.
  30. Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;(1):CD001520.
  31. Nickelsen, T., Demisch, L., Demisch, K., Radermacher, B., and Schoffling, K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 1989;6(4):325-334.
  32. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31.
  33. Middleton, B. A., Stone, B. M., and Arendt, J. Melatonin and fragmented sleep patterns. Lancet 8-24-1996;348(9026):551-552.
  34. Holliman, B. J. and Chyka, P. A. Problems in assessment of acute melatonin overdose. South.Med J 1997;90(4):451-453.
  35. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
  36. Cavallo, A., Ris, M. D., Succop, P., and Jaskiewicz, J. Melatonin treatment of pediatric residents for adaptation to night shift work. Ambul.Pediatr. 2005;5(3):172-177.
  37. Bjorvatn, B., Stangenes, K., Oyane, N., Forberg, K., Lowden, A., Holsten, F., and Akerstedt, T. Randomized placebo-controlled field study of the effects of bright light and melatonin in adaptation to night work. Scand.J Work Environ.Health 2007;33(3):204
  38. Al-Aama, T., Brymer, C., Gutmanis, I., Woolmore-Goodwin, S. M., Esbaugh, J., and Dasgupta, M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int.J.Geriatr.Psychiatry 2011;26(7):687-694.
  39. Appleton RE, Jones AP, Gamble C, et al. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess. 2012;16(40):i-239.
  40. Edwards, B. J., Atkinson, G., Waterhouse, J., Reilly, T., Godfrey, R., and Budgett, R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. Ergonomics 2000;43(10):1501-1513.
  41. Smits MG, Nagtegaal EE, van der Heijden J, et al. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001;16:86-92..
  42. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8:105-10.
  43. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
  44. Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998;13:501-9..
  45. Sandyk R, Tsagas N, Anninos PA. Melatonin as a proconvulsive hormone in humans. Int J Neurosci 1992;63:125-35..
  46. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85..
  47. Molina-Carballo A, Munoz-Hoyos A, Reiter RJ, et al. Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J Pineal Res 1997;23:97-105..
  48. Jan, J. E., Connolly, M. B., Hamilton, D., Freeman, R. D., and Laudon, M. Melatonin treatment of non-epileptic myoclonus in children. Dev.Med Child Neurol. 1999;41(4):255-259.
  49. Rufo-Campos, M. [Melatonin and epilepsy]. Rev Neurol. 2002;35 Suppl 1:S51-S58.
  50. Brueske V, Allen J, Kepic T, and et al. Melatonin inhibition of seizure activity in man [abstract]. Electroencephalog Clin Neurophysiol 1981;51:20P.
  51. Siddiqui MA, Nazmi AS, Karim S, and et al. Effect of melatonin and valproate in epilepsy and depression. Indian J Pharmacol 2001;33:378-381.
  52. Waldron DL, Bramble D, Gringras P. Melatonin: prescribing practices and adverse events. Arch Dis Child. 2005 Nov;90(11):1206-7.
  53. Baandrup L, Lindschou J, Winkel P, Gluud C, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial. World J Biol Psychi
  54. Lui MFG, Chow HKD, Wong WMK, Tsang WNW. Melatonin affects postural control in community-dwelling older adults while dual-tasking: a randomized observation study. J Aging Phys Act. 2018 May 29:1-24.
  55. Scheuer C, Pommergaard HC, Rosenberg J, Gogenur I. Effect of topical application of melatonin cream 12.5% on cognitive parameters: a randomized, placebo-controlled, double-blind crossover study in healthy volunteers. J Dermatolog Treat. 2016 Nov;27(6):488
Constipation Gastrointestinal

Orally, melatonin may cause nausea, abdominal cramps, or mild abdominal pain, diarrhea, constipation, or decreased appetite. Often these symptoms occur during the first few days of treatment and subside after a few days. In some cases, rates of symptoms are similar between melatonin and placebo. Less often, melatonin has been reported to cause abnormal feces, odd taste in the mouth, pouchitis, or reflux esophagitis when used orally. A case of exacerbated symptoms of Crohn disease, including increased diarrhea and abdominal cramps, has been reported for a patient who took oral melatonin 3 mg at bedtime for 4 days. Symptoms resolved within 24 hours of melatonin treatment cessation.

  1. Buscemi, N., Vandermeer, B., Pandya, R., Hooton, N., Tjosvold, L., Hartling, L., Baker, G., Vohra, S., and Klassen, T. Melatonin for treatment of sleep disorders. Evid.Rep.Technol.Assess.(Summ.) 2004;(108):1-7.
  2. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391.
  3. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  4. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  5. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254.
  6. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89.
  7. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32.
  8. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387.
  9. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792.
  10. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi
  11. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614.
  12. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5.
  13. Lancioni GE, O'Reilly MF, Basili G. Review of strategies for treating sleep problems in persons with severe or profound mental retardation or multiple handicaps. Am J Ment Retard 1999;104:170-86.
  14. Calvo, J. R., Guerrero, J. M., Osuna, C., Molinero, P., and Carrillo-Vico, A. Melatonin triggers Crohn's disease symptoms. J Pineal Res 2002;32(4):277-278.
Fatigue Other

There are case reports of body temperature fluctuation and post viral fatigue syndrome associated with melatonin intake.

  1. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
Hepatitis Hepatic

A case of autoimmune hepatitis has been reported for a patient who took melatonin orally to treat insomnia. Melatonin use has also been linked to a few cases of Gilbert's syndrome.

  1. Hong, Y. G. and Riegler, J. L. Is melatonin associated with the development of autoimmune hepatitis? J Clin Gastroenterol 1997;25(1):376-378.
  2. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
Jet lag Dermatologic

Papular skin rash and pruritus has been reported with melatonin use. However, the effect was generally mild and did not require cessation of melatonin treatment, and had similar rates as placebo. Cutaneous flushing, angiokeratoma, and nasal mucosal ulcers have also been reported. Two cases of fixed drug eruption on the genitalia have been reported for patients who used oral melatonin (Nature's Bounty Natural melatonin) for preventing jet lag.

  1. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  2. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254.
  3. Yan W, Li C, Song X, Zhou W, Chen Z. Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Medicine (Baltimore) 2022;101(43):e31411.
  4. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32.
  5. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391.
  6. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89.
  7. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
  8. Bardazzi F, Placucci F, Neri I, D'Antuono A, Patrizi A. Fixed drug eruption due to melatonin. Acta Derm Venereol. 1998 Jan;78(1):69-70.
Myalgia Hematologic

A case of nose bleed has been reported with oral melatonin. Some melatonin preparations contain contaminants that are associated with eosinophilia-myalgia syndrome.

  1. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  2. Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5.
  3. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res To
Myasthenia gravis Genitourinary

Orally, melatonin may increase enuresis in adults and children. In perimenopausal adults, melatonin has caused a resumption of spotting or menstrual flow. Decreased libido has been noted for one patient treated with melatonin 3 mg daily for 8 weeks.

  1. Rossignol, D. A. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann.Clin Psychiatry 2009;21(4):213-236.
  2. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241.
  3. Bendz, L. M. and Scates, A. C. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann.Pharmacother. 2010;44(1):185-191.
  4. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391.
  5. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387.
  6. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792.
  7. Secreto G, Chiechi LM, Amadori A, et al. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 2004;47:11-20.
  8. Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32.
Pain Cardiovascular

Melatonin might increase levels of very low-density lipoprotein (VLDL) cholesterol and triglycerides. Several rare or poorly described cases of abnormal heart rhythms, palpitations, fast heart rate, or chest pain have been reported. However, in these cases, the patients were taking other drugs that could account for the symptoms, and melatonin was not thought to be the cause. Additionally, four cases of elevated left ventricular end-diastolic pressure associated with melatonin intake have been reported.

  1. Wakatsuki, A., Okatani, Y., Ikenoue, N., Kaneda, C., and Fukaya, T. Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women. Maturitas 4-20-2001;38(2):171-177.
  2. Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
  3. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520.
  4. Wade AG, Ford I, Crawford G, 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.
  5. Wade, A. G., Crawford, G., Ford, I., McConnachie, A., Nir, T., Laudon, M., and Zisapel, N. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr.Med.Res.Opin. 2011;27(1):87
  6. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
  7. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
Substance use disorder Ocular/Otic

There are six case reports of pupillary disorder associated with melatonin intake.

  1. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Adverse-effects data: Natural Medicines, Therapeutic Research Center

Dosing

There is no single standardized dose of melatonin, and products vary widely in strength. Many people find that lower doses work as well as higher ones, and taking more does not always help more. Timing often matters as much as the amount, so for sleep timing problems and jet lag it is usually taken in the evening or before bedtime.

The best approach is to follow the directions on the product label and start with the lowest amount that helps. Because the right dose and timing depend on the reason you are using it, check with your pharmacist or doctor for personalized advice, and be especially careful with doses for children.

Pregnancy & Breastfeeding

Melatonin & Pregnancy

Possibly Unsafe

When used orally or parenterally in high doses or with frequent use. High doses of melatonin 75-300 mg daily seem to inhibit ovulation, causing a contraceptive effect. Advise pregnant patients and patients wishing to become pregnant to avoid using melatonin frequently or in high doses. There is insufficient reliable information available about the safety of melatonin in lower doses during pregnancy. Some research shows that taking melatonin 2 mg daily does not affect anterior pituitary hormone levels in females who are not pregnant; this suggests that low doses may not have a contraceptive effect. Other research shows that taking melatonin 3 mg daily during the follicle stimulating stage of in vitro fertilization does not negatively impact pregnancy rates. However, it is not known if melatonin is safe for use throughout pregnancy. Until more is known about the safety of melatonin, avoid using during pregnancy.

  1. Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 1992;74:108-17.
  2. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  3. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
  4. Briggs, Freeman, Yafee. Update Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins, 2001.
  5. Silman RE. Melatonin: a contraceptive for the nineties. Eur J Obstet Gynecol Reprod Biol. 1993;49(1-2):3-9.
  6. Wright, J., Aldhous, M., Franey, C., English, J., and Arendt, J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986;24(4):375-382.
  7. Eryilmaz, O. G., Devran, A., Sarikaya, E., Aksakal, F. N., Mollamahmutoglu, L., and Cicek, N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J.Assist.Reprod.Genet. 2011;28
  8. Batioglu, A. S., Sahin, U., Gurlek, B., Ozturk, N., and Unsal, E. The efficacy of melatonin administration on oocyte quality. Gynecol.Endocrinol. 2012;28(2):91-93.
  9. Nishihara T, Hashimoto S, Ito K, et al. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014;30(5):359-62.
  10. Kim MK, Park EA, Kim HJ, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reprod Biomed Online. 2013;26(1):22-9.
  11. Briggs GG, Freeman RK, Forinash AB, Towers CV. Drugs in Pregnancy and Lactation. 11th ed. Philadelphia, PA: Wolters Kluwer, 2017.

Melatonin & Breastfeeding

Insufficient reliable information

Insufficient reliable information available; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

© 2026 Therapeutic Research Center

Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center

References & further reading

The 118 references that drive our Melatonin monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 1992;74:108-17. DOI
  2. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5. PubMed
  3. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30. PubMed
  4. Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
  5. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8:105-10. PubMed
  6. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-9. PubMed
  7. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  8. Lancioni GE, O'Reilly MF, Basili G. Review of strategies for treating sleep problems in persons with severe or profound mental retardation or multiple handicaps. Am J Ment Retard 1999;104:170-86. PubMed
  9. Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186. PubMed
  10. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  11. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
  12. Lusardi P, et al. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423-7. PubMed
  13. von Bahr C, Ursing C, Yasui N, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects – an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.
  14. Grozinger M, Hartter S, Wang X, et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000 Aug;57:812-3. PubMed
  15. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
Keep reading

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Brand directory

Brands that make products with Melatonin

710 brands in our database make a supplement containing Melatonin.

Product directory

Supplement products with Melatonin

2,891 products in our database contain Melatonin. Open any to see its full ingredient list and every drug interaction we check.

Kids Melatonin Gummies Passiflora Flavored by Natures Craft Gummy Or Jelly 60 Gummy(ies) View ingredients & interactions Kids Melatonin Gummies Strawberry Flavored by Natures Craft Gummy Or Jelly 60 Gummy(ies) View ingredients & interactions Kids Melatonin with Vitamin C by Wonder Labs Tablet Or Pill 90 Chewable Tablet(s) View ingredients & interactions Kids Sleep Chewable Natural Grape Flavor by Mommy's Bliss Tablet Or Pill 35 Chewable Tablet(s) View ingredients & interactions Kids Sleep Gummies by Viva Naturals Gummy Or Jelly 120 Gummie(s) View ingredients & interactions Kids Sleep Gummies Strawberry by Mommy's Bliss Gummy Or Jelly 60 Gummy(ies) View ingredients & interactions Kids Sleep Liquid Natural Grape Flavor by Mommy's Bliss Liquid 4 Fluid Ounce(s) · 120 Milliliter(s) View ingredients & interactions Kids Sleep Quick Drops Mixed Berry by Wink Naturals Liquid 2 Fluid Ounce(s) View ingredients & interactions Kids Sleep Quick Drops Mixed Berry by Wink Kids Liquid 2 Fluid Ounce(s) View ingredients & interactions Kids Sleep Quick Melts Mixed Berry by Wink Naturals Other (e.g. Tea Bag) 30 Melt(s) View ingredients & interactions Kids Sleep Quick Melts Mixed Berry by Wink Naturals Other (e.g. Tea Bag) 30 Melt(s) View ingredients & interactions Kids Sleep Razzberry by OLLY Gummy Or Jelly 60 Gummy(ies) View ingredients & interactions Kids Sleep Razzzberry by OLLY Gummy Or Jelly 50 Gummy(ies) View ingredients & interactions Kids Sleep Tight Raspberry Flavored by Orgain Gummy Or Jelly 60 Gummy(ies) View ingredients & interactions Kids Sleep Tincture Strawberry-Watermelon Natural Flavor by TruHeight Liquid 1 Fluid Ounce(s) · 30 mL View ingredients & interactions Klean Melatonin Natural Raspberry Lemonade Flavor by Klean Athlete Liquid 50 mL · 1.7 Oz(s) View ingredients & interactions Knock Out by InfoWars Life Capsule 30 Capsule(s) View ingredients & interactions Knock-Out by Schiff Tablet Or Pill 50 Tablet(s) View ingredients & interactions Last Thing by Beachbody Capsule 90 Capsule(s) View ingredients & interactions Lean Dream by Fully Flora Capsule 60 Capsule(s) View ingredients & interactions Lean PM by Jacked Factory Capsule 60 Veggie Capsule(s) View ingredients & interactions Lean PM by Jacked Factory Capsule 60 Veggie Capsule(s) View ingredients & interactions Lean PM by Jacked Factory Capsule 60 Veggie Capsule(s) View ingredients & interactions Lean PM by Jacked Factory Capsule 120 Veggie Capsule(s) View ingredients & interactions
Pharmacist Counseling Corner

Melatonin: Common Questions

What is Melatonin used for, and does it work?
People use Melatonin for many reasons, but the evidence varies by use. According to the Natural Medicines database, there is at least some clinical evidence supporting Melatonin for Delayed sleep phase syndrome (DSPS), Non-24-hour sleep wake disorder, Beta blocker-induced insomnia and Emergence delirium. For most other uses it has been studied for, the evidence is currently insufficient to rate. See the graded list on this page, and always confirm with your pharmacist or doctor.
Does Melatonin interact with prescription medications?
Yes. We list 1461 medications with a known interaction with Melatonin. Use the checker above to see how Melatonin interacts with a specific drug.
How are Melatonin interactions rated?
Each interaction is graded major, moderate, or minor based on how clinically significant it is and the strength of the evidence behind it. Major interactions are the most serious and are best avoided, or used only under close professional supervision.
Is it safe to take Melatonin with my medications?
It depends on the specific medication. Some combinations are fine, while others call for monitoring, timing changes, or should be avoided. Check your exact drug above and confirm with your pharmacist or doctor before starting, stopping, or changing anything.
Where does this Melatonin interaction information come from?
Our interaction data is built on the Natural Medicines database — an evidence-graded reference for vitamins, herbs, and supplements — and is reviewed by licensed HelloPharmacist pharmacists, who may add clinical context.
Is Melatonin habit-forming?
Melatonin is not generally considered addictive and does not appear to cause the same dependence as some prescription sleep medicines. Even so, it is best used for short periods and to address a specific sleep issue rather than every night indefinitely.
Will Melatonin knock me out like a sleeping pill?
Not usually. Melatonin tends to help with the timing of sleep more than acting as a strong sedative, so its effect is often mild. It tends to work best for body-clock problems like jet lag or a delayed sleep schedule.
Can children take Melatonin?
Melatonin is sometimes used for sleep problems in children, especially those with certain conditions, but this should be done only under a doctor's guidance. Never start it in a child without first checking with a pediatrician or pharmacist.
Is it safe to take Melatonin during pregnancy or while breastfeeding?
There is not enough reliable safety data, so it is best to avoid Melatonin during pregnancy and breastfeeding unless your doctor specifically recommends it.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Keep exploring

Products that contain Melatonin

A rotating sample of real supplements in our database that list Melatonin — open any to see its full ingredients and every drug interaction we check.

See all 2,891 products with Melatonin →
Where next
Supplement interaction checkerCheck any supplement or product against your medications Drug–drug interactionsCheck two or more of your medications against each other Browse medications A–ZEvery drug we’ve checked against herbs & supplements NDC & pricing lookupFind a drug’s NDCs, packaging and costs Ask a pharmacistFree, personal answer from our licensed team

Have a question about Melatonin?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist