What are the consequences of a melatonin (N-acetyl-5-methoxytryptamine) overdose?

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From the Guidelines

A melatonin overdose typically causes mild symptoms that resolve within 12-24 hours, and while it is generally considered safe, caution is advised due to potential adverse effects, particularly in children and individuals with certain medical conditions. Common effects of a melatonin overdose include drowsiness, headache, dizziness, nausea, vomiting, and irritability, as reported in a review by the National Academy of Sciences 1. In more severe cases, particularly with very high doses, confusion, changes in blood pressure, tremors, and disorientation may occur. Children are more sensitive to melatonin and may experience more pronounced symptoms at lower doses.

Some key points to consider when evaluating the consequences of a melatonin overdose include:

  • The lack of serious adverse effects reported in most studies, including a randomized, placebo-controlled trial that investigated the toxicology of a 28-day treatment with 10 mg melatonin 1
  • The potential for adverse effects such as headaches, somnolence, hypotension, hypertension, gastrointestinal upset, and exacerbation of alopecia areata, particularly at higher melatonin doses 1
  • The association of melatonin with an increase in depressive symptoms, and the need for caution when prescribing to patients taking warfarin and to patients with epilepsy, as reported in various case reports submitted to the World Health Organization 1
  • The importance of proper dosing and storage of melatonin to prevent overdose, particularly in children, and the need for consultation with healthcare providers before use, especially for children or those with medical conditions.

It is essential to note that while melatonin is generally considered safe, extremely large overdoses could potentially cause respiratory depression in rare cases, and anyone experiencing severe symptoms should seek medical attention. To prevent overdose, it is recommended to store melatonin securely away from children, follow recommended dosing (typically 0.5-5mg for adults), and consult healthcare providers before use, especially for children or those with medical conditions. Melatonin works by binding to receptors in the brain that regulate sleep cycles, and excessive amounts overwhelm these receptors, disrupting normal sleep-wake patterns rather than enhancing sleep quality.

From the Research

Consequences of Melatonin Overdose

  • The consequences of a melatonin overdose can vary, but most reported adverse events (AEs) are mild to moderate 2.
  • Common AEs associated with melatonin overdose include daytime sleepiness, headache, dizziness, and hypothermia 2.
  • More severe AEs, such as agitation, fatigue, mood swings, nightmares, skin irritation, and palpitations, have been reported, but are rare 2.
  • A case report of a 16-year-old male who intentionally overdosed on 900mg of melatonin resulted in extreme drowsiness and minimal responsiveness, but the patient regained consciousness 32 hours post-ingestion 3.
  • Another case report of a 66-year-old man who took 24mg of melatonin resulted in lethargy and disorientation, but the patient recovered uneventfully 4.
  • The toxicology of melatonin is not well understood, but it is believed to have a low toxicity potential, although high concentrations of melatonin and its metabolites could have deleterious effects 5.
  • Melatonin overdose can also interact with other drugs, such as benzodiazepines, and may be antagonized by naloxone and flumazenil 4.
  • Supportive measures and vital sign control are crucial in treating melatonin overdose 3.

Potential Risks and Interactions

  • Melatonin may interact with other drugs, such as benzodiazepines, and may be antagonized by naloxone and flumazenil 4.
  • High concentrations of melatonin and its metabolites could have deleterious effects, including nightmares, hypotension, sleep disorders, and abdominal pain 5.
  • Melatonin receptors are present in the periphery and central nervous system, and melatonin may have intracellular actions, which could lead to adverse effects 5.
  • The long-term effects of melatonin overdose are not well understood, and more research is needed to fully understand the potential risks and consequences 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Problems in assessment of acute melatonin overdose.

Southern medical journal, 1997

Research

Toxicology of melatonin.

Journal of biological rhythms, 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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