Melatonin Stats & Data
COc1ccc2ncc(CCNC(C)=O)c2c1DRLFMBDRBRZALE-UHFFFAOYSA-NPharmacology
DrugBankDescription
Melatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B. Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis.
Mechanism of Action
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.
Pharmacodynamics
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
Metabolism
Hepatically metabolized to at least 14 identified metabolites (identified in mouse urine): 6-hydroxymelatonin glucuronide, 6-hydroxymelatonin sulfate, N-acetylserotonin glucuronide, N-acetylserotonin sulfate, 6-hydroxymelatonin, 2-oxomelatonin, 3-hydroxymelatonin, melatonin glucuronide, cyclic melatonin, cyclic N-acetylserotonin glucuronide, cyclic 6-hydroxymelatonin, 5-hydroxyindole-3-acetaldehyde, di-hydroxymelatonin and its glucuronide conjugate. 6-Hydroxymelatonin glucuronide is the major metabolite found in mouse urine (65-88% of total melatonin metabolites in urine).
Absorption
The absorption and bioavailability of melatonin varies widely.
Toxicity
<p>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.</p> <p>Oral, rat: LD50 ≥3200 mg/kg</p>
Indication
Used orally for jet lag, insomnia, shift-work disorder, circadian rhythm disorders in the blind (evidence for efficacy), and benzodiazepine and nicotine withdrawal. Evidence indicates that melatonin is likely effective for treating circadian rhythm sleep disorders in blind children and adults. It has received FDA orphan drug status as an oral medication for this use. A number of studies have shown that melatonin may be effective for treating sleep-wake cycle disturbances in children and adolescents with mental retardation, autism, and other central nervous system disorders. It appears to decrease the time to fall asleep in children with developmental disabilities, such as cerebral palsy, autism, and mental retardation. It may also improve secondary insomnia associated with various sleep-wake cycle disturbances. Other possible uses for which there is some evidence for include: benzodiazepine withdrawal, cluster headache, delayed sleep phase syndrome (DSPS), primary insomnia, jet lag, nicotine withdrawal, preoperative anxiety and sedation, prostate cancer, solid tumors (when combined with IL-2 therapy in certain cancers), sunburn prevention (topical use), tardive dyskinesia, thrombocytopenia associated with cancer, chemotherapy and other disorders.
Receptor Profile
Receptor Actions
Receptor Binding
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Clinically meaningful tolerance to nightly melatonin is not well established. Loss of effect is more often due to suboptimal timing, light exposure, or inappropriate formulation rather than receptor desensitization. Short breaks (several days) may restore perceived efficacy if habituation is suspected. Data quality is limited and largely anecdotal.
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 335 experience reports (335 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 11
Adverse Effects 13
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Strong (n=37) | Heavy (n=31) |
|---|---|---|
| Stimulation | 56.8% | 48.4% |
| Sedation | 54.1% | 45.2% |
| Color Enhancement | 40.5% | 51.6% |
| Anxiety | 32.4% | 25.8% |
| Euphoria | 16.2% | 29.0% |
| Visual Distortions | 27.0% | 25.8% |
| Confusion | 8.1% | 22.6% |
| Music Enhancement | 18.9% | 0% |
| Closed-Eye Visuals | 16.2% | 16.1% |
| Empathy | 16.2% | 9.7% |
| Focus Enhancement | 16.2% | 16.1% |
| Headache | 16.2% | 0% |
| Auditory Effects | 16.2% | 16.1% |
| Memory Suppression | 10.8% | 16.1% |
| Tactile Enhancement | 8.1% | 12.9% |
Subjective Effect Ontology
Experience ReportsStructured effect tags extracted from 335 experience reports using a controlled vocabulary of 220+ canonical effects across 15 domains.
Emotional
Motor
Visual
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 335 experience reports.
Limited tier coverage — most reports fall within the Strong / Heavy range. Effects at other dose levels may not be represented.
| Effect | Strong (n=37) | Heavy (n=31) | |
|---|---|---|---|
| stimulation | → | ||
| sedation | ↓ | ||
| color enhancement | ↑ | ||
| anxiety | ↓ | ||
| euphoria | ↑ | ||
| visual distortions | → | ||
| confusion | ↑ | ||
| music enhancement | — | → | |
| closed-eye visuals | → | ||
| empathy | ↓ | ||
| focus enhancement | → | ||
| headache | — | → | |
| auditory effects | → | ||
| memory suppression | ↑ | ||
| tactile enhancement | ↑ | ||
| body high | ↓ | ||
| introspection | ↑ | ||
| jaw clenching | — | → | |
| dissociation | — | → | |
| nausea | — | → |
Showing top 20 of 25 effects
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers
View effect breakdown
Adverse Effects
| Effect | Strong (n=37) | Heavy (n=31) | Change |
|---|---|---|---|
| Anxiety | -20% | ||
| Confusion | +179% | ||
| Headache | — | 0% | |
| Memory Suppression | +49% | ||
| Jaw Clenching | — | 0% | |
| Nausea | — | 0% | |
| Muscle Tension | — | 0% | |
| Motor Impairment | — | 0% |
Positive Effects
| Effect | Strong (n=37) | Heavy (n=31) | Change |
|---|---|---|---|
| Stimulation | -14% | ||
| Color Enhancement | +27% | ||
| Euphoria | +79% | ||
| Music Enhancement | — | 0% | |
| Empathy | -40% | ||
| Focus Enhancement | 0% | ||
| Tactile Enhancement | +59% | ||
| Body High | -39% | ||
| Introspection | +19% | ||
| Creativity Enhancement | — | 0% |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 262 individual dose entries
Oral (n=172)
Sublingual (n=7)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 150 reports
Harm Reduction
drugs.wikiMelatonin is an endogenous hormone that acts primarily as a chronobiotic, signaling biological night via MT1/MT2 receptors; it is not a general sedative-hypnotic and works best when timing aligns with circadian goals. Immediate-release is usually better for sleep-onset issues, while modified/extended-release can help with sleep maintenance; using the wrong formulation can reduce benefit. For sleep-onset insomnia, many adults respond to 0.5–1 mg taken 30–60 minutes before the intended bedtime; escalating beyond 3–5 mg often adds next-morning grogginess or vivid dreams without improving sleep. For circadian phase shifting (e.g., jet lag or delayed sleep phase), earlier-evening dosing tends to advance sleep timing and late-night dosing can delay it; consistent timing night-to-night is more important than dose size. Alcohol and other CNS depressants increase impairment and can disrupt sleep architecture; avoid combining close to bedtime if possible. Quality control of over-the-counter melatonin products varies widely; independent analyses have found large deviations from labeled dose and occasional contamination (e.g., serotonin), so prefer reputable brands with third-party testing and start low. Fluvoxamine and other strong CYP1A2 inhibitors can greatly increase melatonin levels; conversely, cigarette smoking and high caffeine intake may reduce efficacy. Melatonin can lower blood pressure modestly; those on antihypertensive or anticoagulant/antiplatelet therapy should monitor for dizziness or bruising/bleeding. Use caution in autoimmune conditions or with immunosuppressants due to melatonin’s immunomodulatory actions. Safety data in pregnancy and breastfeeding are limited; non-pharmacologic sleep measures are preferred and medical guidance is advised before use. As with any sleep aid, avoid driving or hazardous tasks for several hours after dosing and especially if feeling drowsy the next morning. If nightly use is ineffective after a week, reconsider timing, formulation, and sleep hygiene (dark environment, reduced evening light/screens) rather than increasing dose.
References
Data Sources
Cited References
Drugs.wiki References
- StatPearls/NCBI Bookshelf: Melatonin (clinical overview, dosing, interactions)
- DrugBank: Melatonin (DB01065) – pharmacology and interactions
- PubChem Compound Summary for Melatonin (CID 896)
- Erland & Saxena 2017. Melatonin content of supplements varies widely; serotonin contamination (open access PMC)