If a man occasionally wakes up after five hours of sleep, is it safe for him to take melatonin even though the night is almost over?

Question

Melatonin, a hormone, is sold over-the-counter in the US and Canada.

Bedtime is a good time to take melatonin

Clinical psychologist Michael Breus writes:

Melatonin is a sleep and body clock regulator, not a sleep initiator. ... Caution should be taken when using melatonin ... It should be taken about 90 minutes before lights out.

An endocrinologist named Richard Wurtman writes:

We investigated whether giving older people melatonin at bedtime as a 'hormone replacement therapy' (i.e. providing them with a dose sufficient to restore nocturnal plasma levels to those of young adults) would also suppress nocturnal awakenings and shorten the time needed to resume sleeping. ... 0.3–1.0 mg, [the doses] which raise plasma melatonin levels to the range that normally occurs nocturnally in young people, was found to help the patients to remain asleep or readily fall back asleep throughout most of the night.

A scenario

Imagine this scenario: Once a month or so, a healthy young adult wakes up after five hours of sleep and has trouble falling back asleep. When this happens, he finds that taking a small dose (between 0.5 mg and 1 mg) of immediate-release melatonin seems to usually help him to fall back asleep an hour later.

My question

Fine; he finds it helpful. But is it safe? Dr. Breus says melatonin should be taken before bedtime. And Dr. Wurtman seems to have studied the use of the tablets close to bedtime — not in the middle of the night. [Edit: Hormones are powerful substances which may have short-term or long-term side effects which we're unaware of. Dr. Breus seems to be implying that melatonin can be used for delayed sleep phase disorder but should not be used for ordinary insomnia. I wonder whether or not it is truly safe to swallow hormones to help deal with these awakenings.]

Postscript

(I added this postscript to my question on May 19.)

I looked at Wikipedia's "Middle-of-the-night insomnia" article today, and noticed that it adds a good insight:

Sleep research conducted already in the 1990s showed that such waking up during the night is in fact a natural sleep pattern that is actually beneficial, rather than a form of insomnia.^[2] If interrupted sleep (called "biphasic sleeping" or "bimodal sleep") is perceived as normal and not referred to as "insomnia", less distress is caused and a return to sleep usually occurs after about one hour.^[3]

Instead of taking a hormone pill (melatonin), perhaps our subject should preferably just wait an hour and then try again to fall back asleep.

Answer 1

According to research published in the British Journal of Clinical Pharmacology and cited below, the serum half-life of immediate release melatonin ranges from 0.54 to 0.67 hours. Assuming you take the melatonin at least 3 hours before you plan to get up, you will have covered around 4 half-lives at the minimum, which would result in a serum level of 6.25% of your peak level. At levels that low, any sleepiness you feel would be mostly due to having just woken up, and not any residual effects of the melatonin. The study also mentions that slow release preparations can keep serum levels high for 5-7 hours, so I would not recommend driving/working after taking one of those.

Aldhous M, Franey C, Wright J, Arendt J. Plasma concentrations of melatonin in man following oral absorption of different preparations. British Journal of Clinical Pharmacology. 1985;19(4):517-521.