Melatonin is a neurohormone primarily synthesized and secreted by the pineal gland in a circadian rhythm, regulated by the suprachiasmatic nucleus (SCN). It plays a crucial role in synchronizing the sleep-wake cycle (circadian rhythm) with the environmental light-dark cycle. The 0.5mg dose is considered a low physiological dose, often used for circadian rhythm entrainment and mild sleep initiation, particularly in the elderly where endogenous production declines.
Adult: 0.5mg to 5mg, taken 30-60 minutes before bedtime. For circadian rhythm disorders, timing is critical (1-2 hours before desired bedtime). 0.5mg is a low starting dose.
Note: Take orally with water, 30-60 minutes before bedtime. Should be taken at the same time each night. Avoid taking immediately after a high-fat meal which can delay absorption. For jet lag, take at bedtime at destination.
Melatonin exerts its primary effects by acting as an agonist at melatonin receptors (MT1 and MT2) in the suprachiasmatic nucleus (SCN) of the hypothalamus. Activation of MT1 receptors promotes sleepiness and vasoconstriction, while MT2 receptor involvement is critical for phase-shifting circadian rhythms. It also has antioxidant and free radical scavenging properties.
Pregnancy: Category N (Not classified by US FDA). Avoid use. Endogenous melatonin plays a role in fetal development; exogenous effects are unknown.
Driving: CAUTION. Do not drive or operate machinery for at least 4-5 hours after ingestion. Melatonin can cause significant drowsiness.
| Fluvoxamine | Markedly increases melatonin levels by inhibiting CYP1A2 and CYP2C19. Risk of excessive sedation. | Major |
| Cimetidine | Increases melatonin concentration by inhibiting CYP1A2. | Moderate |
| CYP1A2 Inducers (e.g., Smoking, Carbamazepine) | Decrease melatonin levels, potentially reducing efficacy. | Moderate |
| Anticoagulants (Warfarin) | May increase INR; monitor coagulation parameters. | Moderate |
| Antidiabetic drugs | May affect glucose metabolism; monitor blood glucose. | Moderate |
| CNS Depressants (Alcohol, Benzodiazepines, Z-drugs) | Additive sedative effect. Increased risk of dizziness and impaired coordination. | Major |
| Immunosuppressants (e.g., Cyclosporine) | Theoretical immunostimulant effect of melatonin may reduce efficacy of immunosuppressants. | Moderate |
| Nifedipine | May inhibit melatonin metabolism. | Moderate |
| Methamphetamine | Antagonizes melatonin-induced vasoconstriction. | Moderate |
Same composition (Melatonin (0.5mg)), different brands: