Melatonin

Safety and precautions

Melatonin is generally considered safe, although a doctor’s supervision is recommended. Melatonin use at recommended doses typically does not lead to dependency, habituation or a drug hangover, all common issues with many pharmaceutical sleep aids.

Side effects or adverse events

Melatonin has a very low toxicity profile and is not associated with significant side effects.¹Yeh CM, Su SC et al. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget. 2017 Aug 9;8(52):90545-90556. 

• No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on cognitive performance among healthy volunteers with full-body application of a cream containing 12.5% melatonin compared to placebo in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²Scheuer C, Pommergaard HC, Rosenberg J, Gögenur I. Effect of topical application of melatonin cream 12.5% on cognitive parameters: a randomized, placebo-controlled, double-blind crossover study in healthy volunteers. Journal of Dermatological Treatment. 2016 Nov;27(6):488-494.
• “I’ve seen melatonin intensify memories of dreaming which can be disruptive to some. In addition, there is a subset of people in whom melatonin seems to induce more wakefulness.”³Dugald Seely. Comment on this review. April 16, 2022.

Interactions with other therapies

Melatonin should be stopped 5 to 7 days before surgery to avoid magnifying the effects of anesthesia.⁴Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Care. New York: Bantam Dell. 2009.

• Increased anesthesia effect of both propofol and thiopental among healthy people using melatonin premedication in a mid-sized RCT;⁵Naguib M, Samarkandi AH et al. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study. Anesthesia and Analgesia. 2006 Dec;103(6):1448-52. our note: a surgical team may choose to use melatonin intentionally to reduce the amount of anesthesia needed during surgery, but this is not common practice. See our commentary in How do experts use melatonin? › 
• Higher sedation scores, extubation time, and recovery time from anesthesia among men with prostate cancer undergoing elective prostatectomy with 6 mg melatonin the night before and 1 hour before surgery compared to placebo in a small RCT⁶Borazan H, Tuncer S, Yalcin N, Erol A, Otelcioglu S. Effects of preoperative oral melatonin medication on postoperative analgesia, sleep quality, and sedation in patients undergoing elective prostatectomy: a randomized clinical trial. Journal of Anesthesia. 2010 Apr;24(2):155-60.

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