What is it?
Melatonin is a hormone found naturally in the body. Melatonin used as medicine is usually made synthetically in a laboratory. It is most commonly available in pill form, but melatonin is also available in forms that can be placed in the cheek or under the tongue. This allows the melatonin to be absorbed directly into the body.
People use melatonin to adjust the body’s internal clock. It is used for jet lag, for adjusting sleep-wake cycles in people whose daily work schedule changes (shift-work disorder), and for helping blind people establish a day and night cycle.
Melatonin is also used for the inability to fall asleep (insomnia); delayed sleep phase syndrome (DSPS); insomnia associated with attention deficit-hyperactivity disorder (ADHD); insomnia due to certain high blood pressure medications called beta-blockers; and sleep problems in children with developmental disorders including autism, cerebral palsy, and intellectual disabilities. It is also used as a sleep aid after discontinuing the use of benzodiazepine drugs and to reduce the side effects of stopping smoking.
Some people use melatonin for Alzheimer’s disease, ringing in the ears, depression, chronic fatigue syndrome (CFS), fibromyalgia, migraine and other headaches, irritable bowel syndrome (IBS), bone loss (osteoporosis), a movement disorder called tardive dyskinesia (TD), epilepsy, as an anti-aging agent, for menopause, and for birth control.
Other uses include breast cancer, brain cancer, lung cancer, prostate cancer, head cancer, neck cancer, and gastrointestinal cancer. Melatonin is also used for some of the side effects of cancer treatment (chemotherapy) including weight loss, nerve pain, weakness, and a lowered number of clot-forming cells (thrombocytopenia).
It is also used to calm people before they are given anesthesia for surgery.
The forms of melatonin that can be absorbed through the cheek or under the tongue are used for insomnia, shift-work disorder, and to calm people before receiving anesthesia for surgery.
Sometimes people apply melatonin to the skin to protect against sunburn.
How effective is it?
Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.
The effectiveness ratings for MELATONIN are as follows:
Likely effective for...
- Sleeping problems in children with autism and intellectual disabilities. Taking melatonin by mouth is helpful for disturbed sleep-wake cycles in children and adolescents with intellectual disabilities, autism, and other central nervous system disorders. Melatonin also appears to shorten the time it takes for to children with developmental disabilities (cerebral palsy, autism, and intellectual disabilities.
- Sleep disorders in blind people.
Possibly effective for...
- Jet lag. Most research shows that melatonin can improve certain symptoms of jet lag such as alertness and movement coordination. Melatonin also seems to improve, to a lesser extent, other jet lag symptoms such as daytime sleepiness and tiredness. But, melatonin might not be effective for shortening the time it takes for people with jet lag to fall asleep.
- Trouble sleeping (insomnia). Melatonin seems to be able to shorten the amount of time it takes to fall asleep, but only by about 12 minutes, according to one research study. Melatonin does not appear to significantly improve “sleep efficiency,” the percentage of time that a person actually spends sleeping during the time set aside for sleeping. Some people say melatonin makes them sleep better, even though tests don’t agree. There is some evidence that melatonin is more likely to help older people than younger people or children. This may be because older people have less melatonin in their bodies to start with.
There is some interest in finding out whether melatonin might help with “secondary insomnia.” This is trouble sleeping that is related to other conditions such as Alzheimer’s disease; depression; schizophrenia; hospitalization; and “ICU syndrome,” sleep disturbances in the intensive care unit. Research to date suggests that melatonin might not help to reduce the time it takes to fall asleep in secondary insomnia, but it might improve sleep efficiency.
- Cluster headaches. Taking 10 mg of melatonin by mouth every evening might reduce the number of cluster headaches. However, taking 2 mg of melatonin at bedtime doesn’t seem to work.
- Reducing anxiety before surgery. Melatonin used under the tongue seems to be as effective in reducing anxiety before surgery as midazolam, a conventional medication. It also seems to have fewer side effects in some people.
- Helping elderly people sleep after they stop taking a type of drug called benzodiazepines. The controlled-release form of melatonin is the type that was shown to work for this.
- Helping decrease symptoms in people who are quitting smoking. A single oral dose of 0.3 mg of melatonin taken 3.5 hours after stopping cigarettes seems to reduce anxiety, restlessness, irritability, depression, and cigarette craving over the next 10 hours.
- Low blood platelets (thrombocytopenia).
- Improving the effectiveness of certain cancer medications used to fight tumors in the breast, lung, kidney, liver, pancreas, stomach, colon, prostate, and decreasing some side effects of cancer treatment.
- Decreasing symptoms of a movement disorder called tardive dyskinesia (TD).
- Decreasing sunburn when applied to the skin in a cream form before going into the sun.
Possibly ineffective for...
- Adjusting sleep schedule in people that do shift work.
Likely ineffective for...
- Depression. There is also some concern that melatonin might worsen symptoms in some people.
Insufficient evidence to rate effectiveness for...
- Epilepsy. There is some evidence that melatonin at bedtime may reduce the number and length of seizures in children with epilepsy. But melatonin should be used cautiously, because melatonin may increase the number of seizures in some people.
- Menopausal symptoms. Limited research suggests that melatonin does not relieve menopausal symptoms. However, melatonin in combination with soy isoflavones might help psychological symptoms associated with menopause.
- Sleep problems associated with attention deficit-hyperactivity disorder (ADHD). Limited research suggests melatonin might improve insomnia in children with ADHD who are taking stimulants. But improved sleep does not seem to decrease symptoms of ADHD.
- Migraine headache. There is some evidence that taking melatonin nightly before bed can prevent episodic migraine headache. When headaches do occur, they are milder and pass more quickly. Some research suggests that melatonin production might be altered in people with migraine.
- Insomnia caused by medications used for high blood pressure (beta-blockers).
- Headache characterized by sudden sharp pain (idiopathic stabbing headache).
- Ringing in the ears (tinnitus).
- Chronic fatigue syndrome (CFS).
- Irritable bowel syndrome (IBS).
- Birth control.
- Other conditions.
More evidence is needed to rate melatonin for these uses.
Melatonin’s main job in the body is to regulate night and day cycles or sleep-wake cycles. Darkness causes the body to produce more melatonin, which signals the body to prepare for sleep. Light decreases melatonin production and signals the body to prepare for being awake. Some people who have trouble sleeping have low levels of melatonin. It is thought that adding melatonin from supplements might help them sleep.
Melatonin is LIKELY SAFE for most adults when taken by mouth short-term or applied to the skin. It can cause some side effects including headache, short-term feelings of depression, daytime sleepiness, dizziness, stomach cramps, and irritability. Do not drive or use machinery for four to five hours after taking melatonin.
Special precautions & warnings:
Pregnancy and breast-feeding: Melatonin is POSSIBLY UNSAFE in pregnancy. Don’t use it. Melatonin might also interfere with ovulation, making it more difficult to become pregnant.
Not enough is known about the safety of using melatonin when breast-feeding. It’s best not to use it.
Children: Melatonin should not be used in most children. It is POSSIBLY UNSAFE. Because of its effects on other hormones, melatonin might interfere with development during adolescence.
High blood pressure: Melatonin can raise blood pressure in people who are taking certain medications to control blood pressure. Avoid using it.
Diabetes: Melatonin might increase blood sugar in people with diabetes. Monitor your blood sugar carefully, if you have diabetes and take melatonin.
Depression: Melatonin can make symptoms of depression worse.
Seizure disorders: Using melatonin might increase the risk of having a seizure.
Be cautious with this combination.
Birth control pills (Contraceptive drugs)
The body makes melatonin. Birth control pills seem to increase how much melatonin the body makes. Taking melatonin along with birth control pills might cause too much melatonin to be in the body.
Some birth control pills include ethinyl estradiol and levonorgestrel (Triphasil), ethinyl estradiol and norethindrone (Ortho-Novum 1/35, Ortho-Novum 7/7/7), and others.
Caffeine might decrease melatonin levels in the body. Taking melatonin along with caffeine might decrease the effectiveness of melatonin supplements.
Taking fluvoxamine (Luvox) can increase the amount of melatonin that the body absorbs. Taking melatonin along with fluvoxamine (Luvox) might increase the effects and side effects of melatonin.
Medications for diabetes (Antidiabetes drugs)
There is some concern that melatonin might increase or decrease blood sugar. Diabetes medications are used to lower blood sugar. By affecting blood sugar, melatonin might decrease or increase the effectiveness of diabetes medications. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.
Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
Medications that decrease the immune system (Immunosuppressants)
Melatonin might increase the immune system. Taking melatonin along with medications that decrease the immune system might decrease the effectiveness of medications that decrease the immune system.
Some medications that decrease the immune system include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others.
Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)
Melatonin might slow blood clotting. Taking melatonin along with medications that also slow clotting might increase the chances of bruising and bleeding.
Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
Nifedipine GITS (Procardia XL)
Nifedipine GITS (Procardia XL) is used to lower blood pressure. Taking melatonin might decrease the effectiveness of nifedipine GITS for lowering blood pressure.
Sedative medications (Benzodiazepines)
Melatonin might cause sleepiness and drowsiness. Drugs that cause sleepiness and drowsiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
Some of these sedative medications include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and others.
Sedative medications (CNS depressants)
Melatonin might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking melatonin along with sedative medications might cause too much sleepiness.
Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.
Verapamil (Calan, Covera, Isoptin, Verelan)
The body breaks down melatonin to get rid of it. Verapamil (Calan, Covera, Isoptin, Verelan) can increase how quickly the body gets rid of melatonin. Taking melatonin along with verapamil (Calan, Covera, Isoptin, Verelan) might decrease the effectiveness of melatonin.
Be watchful with this combination.
Flumazenil (Romazicon) might decrease the effects of melatonin. It is not yet clear why this interaction occurs. Taking flumazenil (Romazicon) along with melatonin might decrease the effectiveness of melatonin supplements.
Herbs and supplements that might slow blood clotting
Melatonin might increase the effect of herbs that slow blood clotting and might increase the risk of bleeding in some people. These herbs include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, red clover, willow, and others.
Herbs and supplements with sleep-promoting (sedative) properties
Using melatonin along with herbs that have sedative properties might increase the effects and side effects of melatonin. Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John's wort, skullcap, valerian, yerba mansa, and others.
There are no known interactions with foods.
The following doses have been studied in scientific research:
- For insomnia:
- 0.3-5 mg at bedtime is a typical dose.
- In children with insomnia due to delayed sleep onset, melatonin 5 mg at 6:00 PM daily.
- In children with developmental disorders (including cerebral palsy, autism, and intellectual disabilities), melatonin 5 mg at 8:00 PM daily. Both immediate-release and sustained-release preparations have been used.
- For jet lag: 0.5-5 mg at bedtime is commonly taken on the arrival day at the destination, continuing for 2-5 days. Low doses of 0.5-3 mg are often used to avoid the hypnotic properties of the higher 4-5 mg doses.
- For tardive dyskinesia (TD): 10 mg daily of a controlled-release formulation.
- As treatment for solid tumors in combination with conventional therapy: 10-50 mg along with radiotherapy, chemotherapy, or interleukin 2 (IL-2). Melatonin is typically started 7 days before the start of chemotherapy and continued throughout full treatment course.
- For treatment of prostate cancer that has spread to other sites (metastatic cancer) and is resistant to triptorelin used alone: 20 mg taken daily has been used in combination with 3.75 mg of triptorelin injected into the muscle every 28 days.
- For prevention and treatment of lowered clot-forming cells (thrombocytopenia) associated with cancer chemotherapy: 20 mg each evening.
- For benzodiazepine withdrawal in elderly people with insomnia: 2 mg of controlled-release melatonin taken at bedtime for 6 weeks (the benzodiazepine dosage is reduced 50% during the second week, 75% during weeks 3 and 4, and stopped during weeks 5 and 6) and continued up to 6 months.
- For prevention of cluster headache: an evening dose of 10 mg.
- For reducing anxiety before surgery in adults: 0.05 mg/kg under the tongue.
- For reducing nicotine withdrawal symptoms: 0.3 mg orally 3.5 hours after stopping smoking.
5-Methoxy-N-Acetyltryptamine, MEL, Melatonina, Mélatonine, MLT, N-acetyl-5-methoxytryptamine, N-Acétyl-5-Méthoxytryptamine, Pineal Hormone.
To learn more about how this article was written, please see the Natural Medicines Comprehensive Database methodology.methodology (http://www.nlm.nih.gov/medlineplus/druginfo/natural/methodology.html).
To see all references for the Melatonin page, please go to http://www.nlm.nih.gov/medlineplus/druginfo/natural/940.html.
- Mutluay R. Elbeg S. Karakus R. et al. The Impact of Melatonin on Glucose Homeostasis. Turkish Journal of Endocrinology and Metabolism 2009;13:52-55.
- Kadhim, HM, Ismail, SH, Hussein, KI, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res 2006;41:189-93.
- Hussain, SA, Khadim, HM, Khalaf, BH, et al. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J 2006;27:1483-8.
- Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32.
- 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.
- Buscemi N, Vandermeer B, Hooton N, et al. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med 2005;20:1151-8.
- van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol 2006;13:55-60.
- Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006;332:385-93.
- Song GH, Leng PH, Gwee KA, et al. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised double blind placebo controlled study. Gut 2005;54:1402-7.
- Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for treatment of sleep disorders. Summary, Evidence Report/Technology Assessment #108. (Prepared by the Univ of Alberta Evidence-based Practice Center, under Contract#290-02-0023.) AHRQ Publ #05-E002-2. Rockville, MD: Agency for Healthcare Research & Quality. November 2004.
Peres MFP, Zukerman E, da Cunha Tanuri F, et al. Melatonin, 3 mg, is effective for migraine prevention. Neurology 2004;63:757.
- 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.
- Pei Z, Pang SF, Cheung RT. Administration of melatonin after onset of ischemia reduces the volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model. Stroke 2003;34:770-5.
- Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res 1998;77:57-61.
- 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.
- Leman ES, Sisken BF, Zimmer S, Anderson KW. Studies of the interactions between melatonin and 2 Hz, 0.3 mT PEMF on the proliferation and invasion of human breast cancer cells. Bioelectromagnetics 2001;22:178-84.
- Nickelsen T, Lang A, Bergau L. The effect of 6-, 9- and 11-hour time shifts on circadian rhythms: adaptation of sleep parameters and hormonal patterns following the intake of melatonin or placebo. Adv Pineal Res 1991;5:303-6.
- Sener G, Satiroglu H, Kabasakal L, et al. The protective effect of melatonin on cisplatin nephrotoxicity. Fundam Clin Pharmacol 2000;14:553-60.
- Tooley GA, Armstrong SM, Norman TR, Sali A. Acute increases in night-time plasma melatonin levels following a period of meditation. Biol Psychol 2000;53:69-78.
- Nathan PJ, Wyndham EL, Burrows GD, Norman TR. The effect of gender on the melatonin suppression by light: a dose response relationship. J Neural Transm 2000;107:271-9.
- 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.
- 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.
- Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.
- 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 Toxicol 1998;11:234-40.
- Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5.
- Burgess HJ, Sletten T, Savic N, et al. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol 2001;91:1214-22.
- Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001;54:339-46.
- Cuzzocrea S, Reiter RJ. Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury. Eur J Pharmacol 2001;426:1-10.
- Hill SM, Collins A, Kiefer TL. The modulation of oestrogen receptor-alpha activity by melatonin in MCF-7 human breast cancer cells. Eur J Cancer 2000;36(Suppl 4):117-8.
- Poeggeler B, Miravalle L, Zagorski MG, et al. Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry 2001;40:14995-5001.
- Andrade C, Srihari BS, Reddy KP, Chandramma L. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry 2001;62:41-5.
- 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.
- Dodge NN, Wilson GA. Melatonin for treatment of sleep disorders in children with developmental disabilities. J Child Neurol 2001;16:581-4.
- Stone BM, Turner C, Mills SL, Nicholson AN. Hypnotic activity of melatonin. Sleep 2000;23:663-9.
- Williams G, Waterhouse J, Mugarza J, et al. Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy. Eur J Clin Invest 2002;32:831-7.
- Cagnacci A, Zanni AL, Veneri MG, et al. Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement. Clin Endocrinol (Oxf) 2000;53:367-72.
- Golombek DA, Escolar E, Burin LJ, et al. Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. Chronobiol Int 1992;9:124-31.
- Pringsheim T, Magnoux E, Dobson CF, et al. Melatonin as adjunctive therapy in the prophylaxis of cluster headache: a pilot study. Headache 2002;42:787-92.
- Citera G, Arias MA, Maldonado-Cocco JA, et al. The effect of melatonin in patients with fibromyalgia: a pilot study. Clin Rheumatol 2000;19:9-13.
- Papezova H, Yamamotova A, Nedvidkova J. Pain modulation role of melatonin in eating disorders. Eur Psychiatry 2001;16:68-70.
- Peled N, Shorer Z, Peled E, Pillar G. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia 2001;42:1208-10.
- Sandyk R. Melatonin and petit-mal epilepsy: an hypothesis. Int J Neurosci 1992;65:83-90.
- Sandyk R, Tsagas N, Anninos PA. Melatonin as a proconvulsive hormone in humans. Int J Neurosci 1992;63:125-35.
- Schapel GJ, Beran RG, Kennaway DL, et al. Melatonin response in active epilepsy. Epilepsia 1995;36:75-8.
- 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.
- Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520.
- Lewy AJ, Ahmed S, Jackson JM, Sack RL. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int 1992;9:380-92.
- 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.
- Nishiyama K, Yasue H, Moriyama Y, et al. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am Heart J 2001;141:E9.
- Briggs, Freeman, Yafee. Update Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins, 2001.
- Djeridane Y, Touitou Y. Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands. Psychopharmacology (Berl) 2001;154:403-7.
- Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;:CD001520.
- Lissoni P, Paolorossi F, Ardizzoia A, et al. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res 1997;23:15-9.
- Naylor S, Gleich GJ. Over-the-counter melatonin products and contamination. Am Fam Physician 1999;59:284, 287-8.
- Wright KP Jr, Myers BL, Plenzler SC, et al. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives. Brain Res 2000;873:310-7.
- Wurtman RJ. Age-related decreases in melatonin secretion--clinical consequences. J Clin Endocrinol Metab 2000;85:2135-6.
- Sivan Y, Laudon M, Kuint J, Zisapel N. Low melatonin production in infants with a life-threatening event. Dev Med Child Neurol 2000;42:487-91.
- Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
- Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology 2000;55:1746-8.
- Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
- Mishima K, Okawa M, Shimizu T, Hishikawa Y. Diminished melatonin secretion in the elderly caused by insufficient environmental illumination. J Clin Endocrinol Metab 2001;86:129-34.
- Salti R, Galluzzi F, Bindi G, et al. Nocturnal melatonin patterns in children. J Clin Endocrinol Metab 2000;85:2137-44.
- Shamir E, Laudon M, Barak Y, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000;61:373-7.
- Nagtegaal JE, Laurant MW, Kerkhof GA, et al. Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome. J Psychosom Res 2000;48:45-50.
- Kumar AM, Tims F, Cruess DG, et al. Music therapy increases serum melatonin levels in patients with Alzheimer's disease. Altern Ther Health Med 1999;5:49-57.
- Shilo L, Dagan Y, Smorjik Y, et al. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int 2000;17:71-6.
- Kovacs J, Brodner W, Kirchlechner V, et al. Measurement of urinary melatonin: a useful tool for monitoring serum melatonin after its oral administration. J Clin Endocrinol Metab 2000;85:666-70.
- Jones MP, Melan MA, Witt-Enderby PA. Melatonin decreases cell proliferation and transformation in a melatonin receptor-dependent manner. Cancer Lett 2000;151:133-43.
- Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178-81.
- Shamir E, Barak Y, Shalman I, et al. Melatonin treatment for tardive dyskinesia: A double-blind, placebo-controlled, crossover study. Arch Gen Psychiatry 2001;58:1049-52.
- Zhdanova IV, Wurtman RJ, Regan MM, et al. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 2001;86:4727-30.
- Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer 1995;71:854-6.
- Erren TC, Piekarski C. Does winter darkness in the arctic protect against cancer? The melatonin hypothesis revisited. Med Hypotheses 1999;53:1-5.
- Kliukiene J, Tynes T, Andersen A. Risk of breast cancer among Norwegian women with visual impairment. Br J Cancer 2001;84:397-9.
- 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.
- Brun J, Claustrat B, Saddier P, Chazot G. Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses. Cephalalgia 1995;15:136-9.
- Sack RL, Brandes RW, Kendall AR, et al. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med 2000;343:1070-7.
- 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.
- 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.
- Drago F, Busa L. Acute low doses of melatonin restore full sexual activity in impotent male rats. Brain Res 2000;878:98-104.
- Spitzer RL, Terman M, Williams JBW, et al. Jet lag: Clinical features, validation of a new syndrome-specific scale, lack of response to melatonin in a randomized, double-blind trial. Am J Psychiatry 1999;156:1392-6.
- 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.
- Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
- Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996;74:1466-8.
- Bubis M, Zisapel N. Modulation by melatonin of protein secretion from melanoma cells: is cAMP involved? Molecular and Cellular Endocrinology 1995;112:169-73.
- Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs. interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196-9.
- Lissoni P, Barni S, Cazzaniga M, et al. Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on Il-2 alone. Oncology 1994;51:344-7.
- Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
- Dreher F, Denig N, Gabard B, et al. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatol 1999;198:52-5.
- Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol 1998;139:332-9.
- Roth JA, Kim B-G, Lin W-L, et al. Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 1999;274:22041-7.
- Lissoni P. Modulation of anticancer cytokines IL-2 and IL-12 by melatonin and the other pineal indoles 5-methoxytryptamine and 5-methoxytryptophol in the treatment of human neoplasms. Ann N Y Acad Sci 2000;917:560-7.
- Lissoni P, Giani L, Zerbini S, et al. Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus Aloe vera in untreatable advanced solid neoplasms. Nat Immun 1998;16:27-33.
- Lissoni P, Bucovec R, Bonfanti A, et al. Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia. J Pineal Res 2001;30:123-6.
- Lissoni P, Tancini G, Barni S, et al. Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer 1997;5:126-9.
- Bellipanni G, Bianchi P, Pierpaoli W, et al. Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study. Exp Gerontol 2001;36:297-310.
- Zhdanova IV, Piotrovskaya VR. Melatonin treatment attenuates symptoms of acute nicotine withdrawal in humans. Pharmacol Biochem Behavior 2000;67:131-5.
- Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432-6.
- Stoschitzky K, Sakotnik A, Lercher P, et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 1999;55:111-5.
- Forsling ML, Wheeler MJ, Williams AJ. The effect of melatonin administration on pituitary hormone secretion in man. Clin Endocrinol (Oxf) 1999;51:637-42.
- Ebadi M, Govitrapong P, Phansuwan-Pujito P, et al. Pineal opioid receptors and analgesic action of melatonin. J Pineal Res 1998;24:193-200.
- Meeking DR, Wallace JD, Cuneo RC, et al. Exercise-induced GH secretion is enhanced by the oral ingestion of melatonin in healthy adult male subjects. Eur J Endocrinol 1999;141:22-6.
- Fraschini F, Cesarani A, Alpini D, et al. Melatonin influences human balance. Biol Signals Recept 1999;8:111-9.
- Nathan PJ, Burrows GD, Norman TR. The effect of age and pre-light melatonin concentration on the melatonin sensitivity to dim light. Int Clin Psychopharmacol 1999;14:189-92.
- Arendt J. Melatonin. BMJ 1996;312:1242-3.
- Brzezinski A. Melatonin in humans. N Engl J Med 1997;336:186-95.
- Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med 1998;30:122-30.
- Jan JE, Freeman RD, Fast DK. Melatonin treatment of sleep-wake cycle disorders in children and adolescents. Dev Med Child Neurol 1999;41:491-500.
- Fischer T, Bangha E, Elsner P, et al. Suppression of UV-induced erythema by topical treatment with melatonin. Influence of the application time point. Biol Signals Recept 1999;8:132-5.
- Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology 1997;195:248-52.
- Leibenluft E, Feldman-Naim S, Turner EH, et al. Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. J Clin Psychiatry 1997;58:383-8.
- Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186.
- Zhdanova IV, Wurtman RJ, Morabito C, et al. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996;19:423-31.
- Nave R, Peled R, Lavie P. Melatonin improves evening napping. Eur J Pharmacol 1995;275:213-6.
- Zhdanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995;57:552-8.
- Dollins AB, Zhdanova IV, Wurtman RJ, et al. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA 1994;91:1824-8.
- Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541-4.
- Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl) 1990;100:222-6.
- Dagan Y, Zisapel N, Nof D, et al. Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur Neuropsychopharmacol 1997;7:157-60.
- Skene DJ, Lockley SW, Arendt J. Melatonin in circadian sleep disorders in the blind. Biol Signals Recept 1999;8:90-5.
- O'Callaghan FJ, Clarke AA, Hancock E, et al. Use of melatonin to treat sleep disorders in tuberous sclerosis. Dev Med Child Neurol 1999;41:123-6.
- Jan JE, O'Donnell ME. Use of melatonin in the treatment of paediatric sleep disorders. J Pineal Res 1996;21:193-9.
- 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.
- Palm L, Blennow G, Wetterberg L. Long-term melatonin treatment in blind children and young adults with circadian sleep-wake disturbances. Dev Med Child Neurol 1997;39:319-25.
- Commentz JC, Uhlig H, Henke A, et al. Melatonin and 6-hydroxymelatonin sulfate excretion is inversely correlated with gonadal development in children. Horm Res 1997;47:97-101.
- Cavallo A, Ritschel WA. Pharmacokinetics of melatonin in human sexual maturation. J Clin Endocrinol Metab 1996;81:1882-6.
- Nordlund JJ, Lerner AB. The effects of oral melatonin on skin color and on the release of pituitary hormones. J Clin Endocrinol Metab 1977;45:768-74.
- Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
- Luboshitzky R, Wagner O, Lavi S, et al. Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment. Clin Endocrinol (Oxf) 1997;47:463-9.
- Haimov I, Lavie P, Laudon M, et al. Melatonin replacement therapy of elderly insomniacs. Sleep 1995;18:598-603.
- Brusco LI, Fainstein I, Marquez M, Cardinali DP. Effect of melatonin in selected populations of sleep-disturbed patients. Biol Signals Recept 1999;8:126-31.
- Sanders DC, Chaturvedi AK, Hordinsky JR. Melatonin: aeromedical, toxicopharmacological, and analytical aspects. J Anal Toxicol 1999;23:159-67.
- Jorgensen KM, Witting MD. Does exogenous melatonin improve day sleep or night alertness in emergency physicians working night shifts? Ann Emerg Med 1998;31:699-704.
- Bregani ER, Lissoni P, Rossini F, et al. Prevention of interleukin-2-induced thrombocytopenia during the immunotherapy of cancer by a concomitant administration of the pineal hormone melatonin. Recenti Prog Med 1995;86:231-3.
- Lissoni P, Barni S, Brivio F, et al. A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia. Oncology 1995;52:360-2.
- Lissoni P, Tancini G, Barni S, et al. The pineal hormone melatonin in hematology and its potential efficacy in the treatment of thrombocytopenia. Recenti Prog Med 1996;87:582-5.
- Lissoni P, Tancini G, Paolorossi F, et al. Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study. J Pineal Res 1999;26:169-73.
- Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699-701.
- Lissoni P, Tisi E, Barni S, et al. Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer. Br J Cancer 1992;66:155-8.
- FDA. List of orphan designations and approvals. Office of Orphan Products Development. Available at: www.fda.gov/orphan/designat/list.htm.
- Lissoni P, Barni S, Cattaneo G, et al. Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies. Oncology 1991;48:448-50.
- Bertino JS, Demuro RL, Blask DE, et al. Absolute bioavailability (F) of oral melatonin (M). Clin Pharmacol Ther 2000;67:106 (abstract PI-72).
- Cagnacci A, Krauchi K, Wirz-Justice A, Volpe A. Homeostatic versus circadian effects of melatonin on core body temperature in humans. J Biol Rhythms 1997;12:509-17.
- Blau JN, Engel HO. A new cluster headache precipitant: increased body heat. Lancet 1999;354:1001-2.
- Peres MF, Seabra ML, Zukerman E, Tufik S. Cluster headache and melatonin. Lancet 2000;355:147.
- Leone M, D'Amico D, Moschiano F, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia 1996;16:494-6.
- DeMuro RL, Nafziger AN, Blask DE, et al. The absolute bioavailability of oral melatonin. J Clin Pharmacol 2000;40:781-4.
- Naguib M, Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg 2000;91:473-9.
- Nurnberger JI Jr, Adkins S, Lahiri DK, et al. Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatr 2000;57:572-9.
- Petrie K, Conaglen JV, Thompson L, Chamberlain K. Effect of melatonin on jet lag after long haul flights. BMJ 1989;298:705-7.
- James SP, Sack DA, Rosenthal NE, Mendelson WB. Melatonin administration in insomnia. Neuropsychopharmacology 1990;3:19-23.
- Sack RL, Lewy AJ, Blood ML, et al. Melatonin administration to blind people: phase advances and entrainment. J Biol Rhythms 1991;6:249-61.
- Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336-9.
- Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
- Dollins AB, Lynch HJ, Wurtman RJ, et al. Effect of pharmacological daytime doses of melatonin on human mood and performance. Psychopharmacol (Berl) 1993;112:490-6.
- 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.
- Valcavi R, Zini M, Maestroni GJ, et al. Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone. Clin Endocrinol (Oxf) 1993;39:193-9.
- Garfinkel D, et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541-44.
- Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5.
- Lissoni P, Pittalis S, Ardizzoia A, et al. Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin. Support Care Cancer 1996;4:313-6.
- Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacol (Berl) 1996;126:179-81.
- Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). A dose response study. Arch Dermatol Res 1996;288:522-6.
- Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239-42.
- Wikner J, Wetterberg L, Rojdmark S. Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion? Eur J Clin Invest 1997;27:374-9.
- Van Den Heuvel CJ, Reid KJ, Dawson D. Effect of atenolol on nocturnal sleep and temperature in young men: reversal by pharmacological doses of melatonin. Physiol Behav 1997;61:795-802.
- Benes L, Claustrat B, Horriere F, et al. Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin. J Pharm Sci 1997;86:1115-9.
- McArthur AJ, Budden S. Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 1998;40:186-92.
- James M, Tremea MO, Jones JS, Krohmer JR. Can melatonin improve adaptation to night shift? Am J Emerg Med 1998;16:367-70.
- Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatr 1998;155:1119-21.
- Wright SW, Lawrence LM, Wrenn KD, et al. Randomized clinical trial of melatonin after night-shift work: efficacy and neuropsychologic effects. Ann Emerg Med 1998 32(3 Pt 1):334-40.
- 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;15:655-6.
- 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.
- Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin, a new clinical approach. Arch Intern Med 1999;159:2456-60.
- Wiid I, Hoal-van Helden E, Hon D, et al. Potentiation of isoniazid activity against Mycobacterium tuberculosis by melatonin. Antimicrob Agents Chemother 1999;43:975-7.
- Wagner J, Wagner ML, Hening WA. Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia. Ann Pharmacother 1998;32:680-91.
- Show more references
- Show fewer references
Last reviewed - 05/30/2014
This copyrighted, evidence-based medicine resource is provided by Natural Medicines Comprehensive Database Consumer Version. Natural Medicines Comprehensive Database disclaims any responsibility related to consequences of using any product. This monograph should not replace advice from a healthcare professional and should not be used for the diagnosis or treatment of any medical condition.
Copyright © 1995 - 2014 Therapeutic Research Faculty
, publishers of Natural Medicines Comprehensive Database
, Prescriber’s Letter
, Pharmacist’s Letter
. All rights reserved. For scientific data on natural medicines, professionals may consult the Professional Version of Natural Medicines Comprehensive DatabaseNatural Medicines Comprehensive Database (http://www.naturaldatabase.com/)