Melatonin
MT1 · MT2

Melatonin is the messenger that tells the body night has fallen and, above all, what time it is. It is a hormone produced by the pineal gland when the retina detects darkness, and from there it acts as a clock that tells the rest of the body when nighttime functions are due and when daytime ones are.

Melatonin is not a sleeping pill; it does not switch you off like a benzodiazepine. It is more like setting the time on a clock than anesthetizing sleep, and that is why it works much better when the problem is when you sleep (jet lag, night shifts, going to bed in the small hours because your internal clock runs late) than when the problem is sleeping at all.

A substance able to “set” the biological clock has a technical name: chronobiotic. Melatonin is one, and it acts on two receptors — MT1 and MT2 — located in the suprachiasmatic nucleus, the region of the hypothalamus that works as the body’s master clock. MT1 is more closely tied to inducing drowsiness; MT2, to shifting the clock’s phase forward or backward. That dual pathway explains why melatonin can, depending on how and when it is taken, help you fall asleep earlier or move your internal clock by several hours.

The marker researchers use to know where your internal clock is at a given moment is called DLMO (dim light melatonin onset, the start of melatonin secretion under dim light). It is the anchor on which almost everything that follows in this guide depends: the ideal dose and the ideal time to take it are not fixed; they depend on where your DLMO sits relative to the time you want to sleep.

Where melatonin has the most solid evidence is not in run-of-the-mill insomnia, but in timing problems: jet lag when crossing several time zones eastward, delayed phase disorder (helplessly falling asleep in the small hours even when you want to sleep earlier), and the misalignment of shift workers. In ordinary insomnia the effect exists but is modest —of the minutes it takes for sleep to come, it trims 4 to 7 on average.

In adults aged 55 or older with insomnia, prolonged-release melatonin (the kind released gradually over several hours rather than all at once) shows a somewhat larger effect than in younger adults —between 10 and 19 minutes less latency versus placebo, depending on the study.

Eastward jet lag is, within this, the best-studied case and where it helps most: traveling east forces the clock to advance, and the human clock (whose natural period is around 24.2 hours) is predisposed to the opposite, to delay. A Cochrane review of ten controlled trials concluded that melatonin is markedly effective at preventing or reducing jet lag, especially on trips of five time zones or more eastward.

For the traveling athlete, the scenario is basically the same transmeridian jet lag as any traveler’s, with the difference that the cost of arriving desynchronized at a competition is higher. Melatonin does not directly improve strength or maximal oxygen uptake —no serious study supports that—; what it does is help resynchronize sleep and, with it, daytime alertness and perceived fatigue in the days after the flight. A trial in athletes who flew ten time zones eastward and took 5 mg over the following four days (Edwards et al., 2000, Ergonomics, PMID 11083138) recorded less fatigue and more alertness in the afternoon versus placebo.

In primary insomnia in adults —that is, without an underlying timing disorder but of another kind— according to several meta-analyses used here only as context and never as primary evidence, it ranges between 4 and 7 minutes less latency versus placebo. It is a real but small reduction; one of those meta-analyses literally called it “clinically insignificant.” The partial exception is adults aged 55 or older: there, prolonged-release (2 mg, the formulation of the authorized medicine Circadin®) has shown reductions of between 9 and 19 minutes in its five pivotal trials (Lemoine 2007, Wade 2007, Luthringer 2009, Wade 2010 and Wade 2011), with the effect most marked in those over 65. It is worth knowing, and it is developed in the evidence section, that almost all of those trials are funded by the patent holder.

Melatonin is not a cognitive stimulant: there is no evidence that it improves memory, attention, or mental performance in someone whose sleep is well synchronized. The cognitive benefit that does appear in studies is always indirect; it occurs when there is an underlying timing misalignment (jet lag, shifts) and melatonin helps correct it; by improving sleep and resetting the clock, next-day cognitive performance improves along with it. Attributing a direct effect on cognition to it, without that prior misalignment, has no support.

It makes the most sense for you if you fly frequently across time zones, work rotating shifts, or struggle to fall asleep before 2 or 3 in the morning no matter how hard you try. Outside those timing patterns, the benefit you can expect is more modest.

Important: in children, melatonin is not a self-care supplement. There is solid evidence for its use in childhood insomnia within autism spectrum disorder, but always under medical supervision, never as a decision parents make on their own —this is developed in the evidence section and, above all, in the contraindications section.

Here is a principle worth committing to memory because it runs against what is usually assumed about supplements: less is usually more. The small dose, similar to what your body produces naturally, performs as well as or better than a dose ten times larger, and without the side effect that does appear with the high dose: melatonin keeps circulating in the blood well into the day, which translates into residual morning drowsiness.

Commercial products, however, are usually sold in doses of 1 to 10 mg —far above that physiological dose.

When you take it matters more than how much. To advance the clock —the case of eastward jet lag or a delayed internal clock— the studied time is the afternoon, several hours before the desired bedtime. To delay the clock —for example, after a westward flight— the studied time is shortly after waking, not at night.

The research underpinning the “less is more” axis is from Zhdanova et al. (2001, Journal of Clinical Endocrinology & Metabolism, DOI: 10.1210/jcem.86.10.7901, PMID 11600532), in adults aged 50 or older. The physiological dose of 0.3 mg restored sleep efficiency without inducing hypothermia or keeping melatonin elevated during daylight hours, something that did happen with the 3 mg dose. The underlying explanation is that the body already has a well-calibrated system for producing melatonin in the amounts it needs; adding much higher doses does not perfect that system, it simply floods it for more hours than is desirable.

That timing matters so much has an uncomfortable side: taking it at the wrong time not only stops helping, it can make things worse. In a trial with 52 cabin crew members (Petrie et al., 1993, Biological Psychiatry, PMID 8513037), those who took melatonin before the flight ended up worse than with placebo, while those who took it after arriving did improve. The same substance, the same dose: only the time changed.

In adults aged 55 or older with insomnia, the prolonged-release formulation (2 mg, which releases melatonin gradually over 8 to 10 hours, mimicking the natural profile) is taken one to two hours before bed, and is authorized by the European Medicines Agency for up to 13 weeks of continuous use in that specific indication.

A significant part of the melatonin you take by mouth is lost before it reaches the blood: the liver processes and removes a good portion of it on its first pass. This is not a flaw of the supplement; it is simply the reason the usual oral doses (1 mg or more) are higher than the amount your body produces naturally in a night.

The oral bioavailability of melatonin is around 15%, with a fairly wide range (9-33%) depending on the study and the person. First-pass (hepatic) metabolism removes about 85% of the dose. That variability is one of the reasons two people taking the same pill can notice different effects.

There are presentations that avoid part of that first pass —sublingual or spray— absorbed directly through the lining of the mouth, with a faster onset of effect and greater systemic bioavailability than the conventional oral route. There is still (06/2026) no systematic analysis of how closely the actual dose of these commercial sublingual products matches what the label states.

No, and here melatonin has a more serious problem than most supplements: what the label says and what is inside the bottle do not always match, and sometimes the difference is enormous. An analysis of commercial products (Erland and Saxena, 2017) found actual contents ranging from 83% below the stated amount to 478% above, with more than 7 out of 10 products outside a reasonable margin (±10%) relative to their label. Another analysis focused only on gummies (the format most used in children) found that 22 of 25 products analyzed (88%) had inaccurate labeling, with actual contents between 74% and 347% of the stated amount. One of those gummies, on top of that, contained no detectable melatonin, but rather CBD.

This variability is not an isolated case or one particular brand with bad luck: it is a documented, recurring pattern in the OTC (over-the-counter) melatonin supplement market, made worse because, being a food supplement in most countries, it is not required to undergo the same prior content verification as a medicine. The problem is especially concentrated in chewable formulations —precisely the ones that, by their candy-like look and taste, are also those that cause the most accidental ingestions in children (developed in the evidence section and in contraindications).

Given the labeling problem described earlier, with melatonin the independent verification seals carry more weight than with most supplements —for example, USP Verified or NSF, which check that the actual content matches what is declared. In the sports context, where avoiding banned substances also matters, examples of that kind of seal are Informed Sport or NSF Certified for Sport.

On its status in sport: melatonin is not included in the 2025 Prohibited List of the World Anti-Doping Agency (WADA), neither in nor out of competition. It is worth checking each season, since the list is reviewed annually, but as of this guide there is no restriction.

A selection of randomized, double-blind, placebo-controlled trials —the standard this site requires. There are 25 main trials in the dossier behind this guide, of which only a handful are later than 2020: melatonin is, paradoxically, one of the worst-funded supplements for new research despite decades of use, so much of the reference evidence is already fifteen or twenty years old. That does not invalidate it —several of those trials remain, today, the best data available— but it is worth knowing when reading them.

Sletten et al. (2018, PLoS Medicine) —the modern reference trial in delayed sleep-wake phase disorder, already described in the “What is it for?” section: 116 adults, 0.5 mg of fast-release melatonin one hour before the desired bedtime, combined with behavioral guidance, for four weeks. Sleep came 34 minutes earlier than with placebo and notable clinical improvement nearly doubled (52.8% versus 24.0%). Public funding.

Sack et al. (2000, New England Journal of Medicine, DOI: 10.1056/NEJM200010123431503) —the pivotal trial in the non-24-hour rhythm of totally blind people, a rare disorder in which the internal clock, without the light signal to anchor it, free-runs. Seven blind people with free-running rhythms received 10 mg of melatonin one hour before their preferred sleep time; six of the seven managed to enter a 24-hour cycle, and that adjustment held even when the dose was reduced to 0.5 mg a day. The sample is small because the disorder itself is rare, but the result was clear enough that this study remains, 25 years later, the reference underpinning the use of melatonin in this context. Public funding (NIH), no commercial ties.

On jet lag in travelers and athletes: the largest-sample trial to date (Suhner et al., 1998, Chronobiology International) compared several doses in 320 travelers who crossed 6 to 8 time zones eastward. The 5 mg fast-release dose was the most effective for latency, sleep quality, drowsiness, and fatigue; curiously, the 2 mg prolonged-release version was the least effective of those tested in that particular context —a reminder that the sleep-maintenance formulation is not necessarily the best for resynchronizing a shifted clock.

Two recent clinical guidelines reach different conclusions about this same body of evidence: the 2017 US guideline leans, with a weak recommendation, toward not using melatonin for insomnia in adults; the 2023 European guideline does allow the use of prolonged-release for up to three months in those over 55, also with a moderate strength of recommendation. The difference is not that one guideline is right and the other wrong —it is that they weigh the same modest finding differently.

Before reading this: all the evidence that follows is presented for its scientific value, not as an invitation to pediatric self-medication. Melatonin in children must always be the decision and follow-up of a healthcare professional, never a decision made at home, and this is stressed in the contraindications section.

The pivotal trial underpinning the European authorization of the pediatric medicine Slenyto® (Gringras et al., 2017, Journal of the American Academy of Child & Adolescent Psychiatry, DOI: 10.1016/j.jaac.2017.09.414) included 125 children aged 2 to 17, the vast majority with an ASD diagnosis, treated with pediatric prolonged-release melatonin for 13 weeks. Total sleep time increased about 32 minutes more than with placebo, and treatment dropout was notably lower in the treated group (15.0%) than in the placebo group (32.3%) —an indirect but relevant indicator of how the families experienced it. A subsequent two-year follow-up by the same team found no effects on growth, weight, or pubertal development. Here too the sponsor is Neurim, holder of the product’s patent, and several authors are employees or consultants of the company —the same structural bias as in the older-adults indication.

Almost all the pivotal prolonged-release evidence depends on a single manufacturer. The trials underpinning both the older-adults indication (Circadin) and the pediatric autism one (Slenyto) are funded, almost entirely, by the company that holds the patent. There is still no independent pivotal trial replicating those results without that funding behind it —a real gap, not an unfounded suspicion.

The quality of over-the-counter products remains an unresolved problem, as seen in the formulations section: the variability of actual content versus labeling is high and documented in several independent analyses, and there is no sign that it has been corrected in recent years.

A large, recent jet-lag trial with a real flight is missing. The Cochrane review underpinning the recommendation for use in jet lag is from 2002, last updated in 2008; there is no large, randomized, double-blind trial later than 2020 that has repeated or updated it with real flights.

There is no direct comparison between immediate- and prolonged-release in insomnia of older adults. Each formulation has its own trials, but no study has pitted them head-to-head in the same population to find out which works better in practice.

In the short term, in healthy adults, melatonin has a good safety profile. Even so, there are situations in which it is wise to talk to a doctor before taking it —and one, above all, in which the decision should never be made at home without supervision:

• Children and adolescents. However many over-the-counter products with a harmless appearance exist, melatonin in minors is not self-care. Its pediatric use, including in the autism context where there is solid clinical evidence, must always be prescribed and supervised by a healthcare professional.
• Pregnancy and breastfeeding. It is not recommended, due to a lack of sufficient clinical data —not because firm proof of risk exists, but because the evidence needed to rule it out with confidence is not there.
• Treatment with fluvoxamine (an antidepressant). This combination is documented and is one of the most relevant interactions in this whole guide: fluvoxamine can multiply melatonin blood levels by 17. While on fluvoxamine, medical assessment before adding melatonin is necessary.
• Driving and operating machinery. The effect can persist for several hours; the usual caution period is the 4-5 hours after taking it.

As with any supplement, the above is information, not a substitute for a doctor’s assessment, especially with other ongoing medication or a diagnosed chronic illness.

There is also a group of situations where clinical prudence recommends prior consultation, even if the evidence of direct risk is weaker or less studied: autoimmune diseases (melatonin has an immunomodulatory role that is not fully characterized), hepatic insufficiency (its metabolism is hepatic), epilepsy (the risk signal is weak and the data contradictory, but it exists), and coagulation disorders or treatment with anticoagulants such as warfarin, where it is advisable to monitor the INR if combining them under medical supervision.

Drug interactions to keep in mind (information, not a substitute for medical assessment in the case of treatment with any of these drugs):

A curiosity worth knowing because it changes how its “safety” is perceived: the same molecule has completely different statuses depending on the country. In the United States it is bought over the counter in any supermarket; in the United Kingdom and Japan it is a medicine dispensed only with a doctor’s prescription. In the European Union it is, in general, a food supplement with dose limits that vary widely from one country to another. That disparity does not reflect differences in the available scientific evidence —it is the same in every country— but different regulatory decisions about where to set the threshold of “medicine” versus “supplement.”