hormone · for anxiety
Melatonin
Meant to work through melatonin receptors and the brain’s calming system.
Say that in clinical terms
Proposed anxiolytic action is thought to work via melatonin receptors (MT1/MT2) and downstream GABAergic modulation.
How strong is the research?
No Benefit evidence
No improvement in anxiety scores in postmenopausal women.
Low-quality evidence
1 paper read, 1 against.
Tested as: no consistent trial evidence for generalized/chronic anxiety in a general population; the well-studied form is a single dose given before surgery for situational (procedural) anxiety, which is a different question — see needs_new_symptom
Before you take it
- No NIH/IOM Tolerable Upper Intake Level (UL) has been established for melatonin; standard OTC doses range from 0.5 mg to 10 mg but pharmacological effects are seen well below 1 mg.
- CYP1A2 major interaction: melatonin is primarily metabolized by CYP1A2; co-administration of fluvoxamine (Luvox) increases melatonin AUC ~17-fold and Cmax ~12-fold, such that a standard 1.5 mg dose can behave pharmacokinetically like 18–25 mg — risk of dangerous over-sedation; ciprofloxacin and estrogen-containing oral contraceptives also substantially elevate melatonin plasma levels.
- Anticoagulant interaction: melatonin has been shown to reduce plasma coagulation factors and may amplify the anticoagulant effect of warfarin and other blood-thinning agents; patients on anticoagulation therapy require INR monitoring if melatonin is added.
- Additive CNS depression when co-administered with benzodiazepines, z-drugs (zolpidem, zaleplon), alcohol, or opioids.
- Pregnancy and lactation: melatonin crosses the placenta and is excreted in breast milk; developmental safety data are insufficient and it is generally not recommended during pregnancy or breastfeeding without medical supervision.
- Daytime sedation and impaired alertness have been reported, particularly at doses above 2 mg; higher-end doses in common OTC products (5–10 mg) substantially increase next-day somnolence risk.
- Pediatric chronic use: long-term effects on pubertal timing have not been definitively ruled out; evidence base for extended use in children remains limited.
- OTC label accuracy concern: a 2023 analysis of 25 melatonin gummy products found actual content ranged from 74% to 347% of the labeled dose, and 26% of products also contained unlabeled serotonin.