Melatonin
Melatonin Uses, Dosage, Side Effects, Food Interaction and all others data.
Melatonin and melatonin agonists inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the melatonin receptor antagonist luzindole, which suggests that melatonin activates a presynaptic melatonin receptor.
Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag.MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions
| Trade Name | Melatonin |
| Availability | Rx and/or OTC |
| Generic | Melatonin |
| Melatonin Other Names | Melatonin, Melatonina, Mélatonine |
| Related Drugs | amitriptyline, lorazepam, zolpidem, diphenhydramine, Ativan, Ambien |
| Type | |
| Formula | C13H16N2O2 |
| Weight | Average: 232.2783 Monoisotopic: 232.121177766 |
| Protein binding | n/a |
| Groups | Approved, Nutraceutical, Vet approved |
| Therapeutic Class | Hormone preparations for other uses, Oral nutritional preparations |
| Manufacturer | Colonis Pharma Ltd |
| Available Country | United Kingdom, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Melatonin is used for numerous conditions but is showing the most promise in short-term regulation of sleep patterns, including jet lag.
Insomnia: Melatonin helps to induce sleep in people with-
- Disrupted circadian rhythms (such as those suffering from jet lag or poor vision or those who work the night shift)
- Low melatonin levels (such as some elderly and individuals with schizophrenia)
- Children with learning disabilities who suffer from insomnia.
Osteoporosis: Melatonin stimulates cells called osteoblasts that promote bone growth.
In Menopause:
Melatonin helps peri- or postmenopausal women to regulate sleep patterns.
Eating disorders: Melatonin levels may play a role in the symptoms of anorexia.
Sarcoidosis:
Sarcoidosis is an inflammatory disease that affects multiple organs in the body, but mostly the lungs and lymph glands.
Attention Deficit Hyperactivity Disorder (ADHD): It may be effective in managing sleep disturbances in children with this condition
Melatonin is also used to associated treatment for these conditions: Insomnia
How Melatonin works
Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.
Dosage
Melatonin dosage
Adult-
Insomnia: 3-6 mg one hour before bedtime
Jet lag: 0.50 to 5 mg one hour prior to bedtime at final destination or, 1 to 5 mg 1 hour before bedtime for 2 days prior to departure and for 2 to 3 days upon arrival at final destination.
- Eastbound travel: Take a preflight early evening treatment followed by treatment at bedtime for 4 days after arrival.
- Westbound travel: Take for 4 days at bedtime when in the new time zone.
Sarcoidosis:
20 mg per day for 4 to 12 months.
Depression: 0.125 mg twice in the late afternoon, each dose 4 hours apart.
Difficulty falling asleep: 5 mg 3 to 4 hours before an imposed sleep period over a 4-weeks period.
Children-
6 months to 14 years of age with sleep disorders: 0.30 mg/day
Side Effects
Increased seizure activity; drowsiness, headache. Disruption of normal circadian rhythm. May worsen symptoms for individuals with depression.
Toxicity
Generally well-tolerated when taken orally. The most common side effects, day-time drowsiness, headache and dizziness, appear to occur at the same frequency as with placebo. Other reported side effects include transient depressive symptoms, mild tremor, mild anxiety, abdominal cramps, irritability, reduced alertness, confusion, nausea, vomiting, and hypotension. Safety in Adults: Evidence indicates that it is likely safe to use in oral and parenteral forms for up to two months when used appropriately. Some evidence indicates that it can be safely used orally for up to 9 months in some patients. It is also likely safe to use topically when used appropriately. Safety in Children: Melatonin appeared to be used safely in small numbers of children enrolled in short-term clinical trials. However, concerns regarding safety in children have arisen based on their developmental state. Compared to adults over 20 years of age, people under 20 produce high levels of melatonin. Melatonin levels are inversely related to gonadal development and it is thought that exogenous administration of melatonin may adversely affect gonadal development. Safety during Pregnancy: High doses of melatonin administered orally or parenterally may inhibit ovulation. Not advised for use in individuals who are pregnant or trying to become pregnant. Safety during Lactation: Not recommended as safety has not be established.
Oral, rat: LD50 ≥3200 mg/kg
Precaution
Caffeine and fluvoxamine may increase the effects of melatonin, while melatonin may decrease the antihypertensive effect of nifedipine.
Interaction
Antidepressant Medications: Melatonin reduces the antidepressant effects of desipramine and fluoxetine. In addition, fluoxetine leads to measurable depletion of melatonin in people.
Antipsychotic Medications: People with schizophrenia and tardive dyskinesia taking antipsychotic medications with melatonin has significantly reduced mouth movements compared to those who did not take the supplements.
Benzodiazepines: The combination of melatonin and triazolam improves sleep quality. In addition, there have been a few reports suggesting that melatonin supplements may help individuals stop using long-term benzodiazepine therapy.
Blood Pressure Medications: Melatonin may reduce the effectiveness of blood pressure medications like methoxamine and clonidine. In addition, calcium channel blockers (such as nifedipine, verapamil, diltiazem, amlodipine, nimodipine, felodipine, nisoldipine, and bepridil) may decrease melatonin levels. Use of beta-blockers (propranolol, acebutolol, atenolol, labetolol, metoprolol, pindolol, nadolol, sotalol, and timolol) may reduce melatonin production in the body.
Blood-Thinning Medications, Anticoagulants: Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin.
Interleukin 2: In one study of 80 cancer patients, use of melatonin in conjunction with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs such as ibuprofen may reduce the levels of melatonin in the blood.
Steroids and Immunosuppressant Medications: People should not take melatonin with corticosteroids or other medications used to suppress the immune system because the supplement may cause them to be ineffective.
Tamoxifen: Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit certain patients with breast and other cancers.
Other Substances: Caffeine, tobacco, and alcohol can all diminish levels of melatonin in the body while cocaine and amphetamines may increase melatonin production.
Food Interaction
- Avoid alcohol. Ingesting alcohol may reduce the effects of melatonin.
- Take after a meal. Administration of melatonin after eating slows the absorption and reduces the Cmax of melatonin.
[Minor] Oral caffeine may significantly increase the bioavailability of melatonin.
The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism.
After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%.
The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6).
The greatest effect was seen in subjects with the *1F<*1F genotype (n=7), whose melatonin Cmax increased by 202%.
The half-life did not change significantly.
The clinical significance of this interaction is unknown.
Melatonin Drug Interaction
Moderate: diphenhydramine, duloxetine, escitalopram, pregabalin, alprazolam, sertralineUnknown: aspirin, loratadine, ubiquinone, omega-3 polyunsaturated fatty acids, fluticasone nasal, polyethylene glycol 3350, bifidobacterium infantis / lactobacillus acidophilus, montelukast, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine
Melatonin Disease Interaction
Elimination Route
The absorption and bioavailability of melatonin varies widely.
Half Life
35 to 50 minutes
Pregnancy & Breastfeeding use
Information regarding safety and efficacy in pregnancy and lactation is not available.
Contraindication
Melatonin should not be used by patients who have autoimmune diseases.
Acute Overdose
There is little or no evidence of any major toxicities with melatonin, even at high doses.
Storage Condition
Store in a cool & dry place, protected from light & moisture.
Innovators Monograph
You find simplified version here Melatonin
Melatonin contains Melatonin see full prescribing information from innovator Melatonin Monograph, Melatonin MSDS, Melatonin FDA label
FAQ
What does Melatonin used for?
Melatonin is most commonly used for insomnia and improving sleep in different conditions. For example, it is used for jet lag, for adjusting sleep-wake cycles in people whose daily work schedule changes (shift-work disorder), and for helping people establish a day and night cycle.
Is taking Melatonin safe?
Melatonin is generally safe for short-term use. Unlike with many sleep medications, with melatonin you are unlikely to become dependent, have a diminished response after repeated use (habituation), or experience a hangover effect. The most common melatonin side effects is headache.
Why is it bad to take Melatonin every night?
Taking the recommended dose of Melatonin may increase your blood melatonin levels up to 20 times more than normal and give you side effects that include: Excessive sleepiness. Headache. Dizziness.
Is Melatonin a sleeping pill?
Melatonin is a hormone and dietary supplement commonly used as a sleep aid.
What happens if you take Melatonin and stay awake?
Melatonin will stay in the body for about 5 hours. If you stay awake during this time, you're more likely to feel aftereffects like drowsiness. That's why it's recommended to avoid driving or using heavy machinery within 5 hours of taking it.
What are the side effects of Melatonin?
Melatonin has been used safely for up to 2 years in some people. However, 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.
Is melatonin good for anxiety?
Melatonin, a hormone produced by your body, has been shown to improve symptoms of anxiety. Melatonin supplementing with melatonin for anxiety can improve sleep quality, regulate circadian rhythm, and ease negative feelings associated with anxiousness.
What is a safe Melatonin dose?
According to Michael Grandner, director of the Sleep and Health Research Program at the University of Arizona, “Melatonin is very safe if taken in normal doses,” which is anything between 0.5 mg and 5 mg.
Is Melatonin bad for liver?
In several clinical trials, Melatonin was found to be well tolerated and not associated with serum enzyme elevations or evidence of liver injury. Despite wide scale use, Melatonin has not been convincingly linked to instances of clinically apparent liver injury.
What medications should not take with Melatonin?
You should not take Melatonin with corticosteroids or other medications used to suppress the immune system because the supplement may cause them to be ineffective.
Why does Melatonin make me dream?
The more Melatonin in your body, the more it may be contributing to memory processes happening during sleep. Because of this, you may have more episodes of vivid dreams that help your brain establish how these memories relate to your understanding of reality while you're awake.
How do I quit taking Melatonin?
You should not get any harmful discontinuation or withdrawal effects if you stop taking Melatonin. However, you may get your old symptoms back. If you are on a high dose, then the doctor may wish to reduce the dose slowly before stopping it completely.
What foods have melatonin?
Foods With Melatonin
- Tart Cherries
- Goji Berries
- Eggs
- Milk
- Fish
- Nuts
Why does Melatonin make me wake up in the middle of the night?
Melatonin is a hormone your brain makes naturally to control your sleep cycle. The process is tied to the amount of light around you. Your melatonin level usually starts to rise after the sun sets and stays high during the night. It drops in the early morning, which helps you wake up.
Can I have a glass of wine with Melatonin?
It is not safe to drink alcohol while taking Melatonin. Alcohol interferes with the effectiveness of medications and supplements, and melatonin is no exception. Alcohol can either weaken or strengthen the effects of Melatonin.
Does Melatonin help with belly fat?
According to a new medical study, this sleep hormone may also have the ability to help individuals lose weight. Melatonin has been found to speed up the production of fat burning and result in a higher metabolism.
What is Melatonin good for besides sleep?
Melatonin may improve sleep, eye health, seasonal depression, HGH levels and GERD. Doses of 0.5–10 mg per day appear to be effective, though it's best to follow label recommendations. Melatonin is safe and associated with minimal side effects, but may interact with some medications.
What happens if you stay awake after taking Melatonin?
Staying awake after taking a sleeping pill can cause dangerous side effects to surface, including hallucinations and lapses in memory.
How much Melatonin can I take?
The maximum recommended dose of Melatonin is 10 milligrams. Several factors, such as age, body weight, and sensitivity to melatonin may affect the recommended dosage. The dose also depends on the type and severity of the sleep problem. Certain drugs may also affect the way melatonin is metabolized.
Does melatonin hurt my kidneys?
Melatonin reduces the oxidative induced brain, heart, kidney, and liver damage in rats. These effects of Melatonin are related to scavenging of a variety of toxic oxygen and nitrogen based reactants and stimulation of antioxidative enzymes (1-5).
Does Melatonin weaken my immune system?
Melatonin stimulates the production of progenitor cells of granulocytes and macrophages and of NK cells. Production of IL-2, IL-6 and IL-12 is stimulated by melatonin. Increased T-helper production, particularly of CD4+ cells, occurs after melatonin supplementation. Melatonin decreases CD8+ cells.
Does Melatonin help with inflammation?
Melatonin has been shown to possess anti-inflammatory effects, among a number of actions. Melatonin reduces tissue destruction during inflammatory reactions by a number of means. Thus Melatonin, by virtue of its ability to directly scavenge toxic free radicals, reduces macromolecular damage in all organs.
What does Melatonin do to my body?
Melatonin is a hormone that your brain produces in response to darkness. It helps with the timing of your circadian rhythms (24-hour internal clock) and with sleep. Being exposed to light at night can block melatonin production. Research suggests that melatonin plays other important roles in the body beyond sleep.
Is Melatonin bad for me long-term use?
Short-term use of Melatonin may not be harmful but there is insufficient evidence on its long-term safety, according to the National Center for Complementary and Integrative Health.
