The M Word

September 17, 2021

As I wander through the aisles of my local pharmacy, my puffy and bloodshot eyes do a poor job of scanning the products. It should be illegal to stay awake this long. 15 hours ago I woke up in Frankfurt, Germany at 6am, after getting only a few hours of restless sleep in a stuffy hotel room. A few cups of coffee and one plane ride later, and it’s 5pm Denver time. There seems to be a thin line between sleeplessness and drunkenness to which I’m coming dangerously close. I still have around four or five hours to go before I can go to sleep, but the siren song of my bed is becoming increasingly more tempting as the night… ahem - I mean, day, drags on. I just have to find one thing before I go to sleep. One thing that will hopefully make the process of changing my brain back to Colorado time a little less painful. 

The human circadian rhythm will adjust about an hour each day to re-align with whatever day/night cycle your eyeballs currently occupy. I say eyeballs specifically because this brain rhythm is dictated by the light, or lack of light, which makes its way into the brain through the eyes. Frankfurt is eight hours ahead of Denver, so if my circadian clock adjusts about one hour a day, I’m looking at eight days before I become re-regulated to my current time zone. But I’m hoping I can find something in this pharmacy to bring my eight days down to, let’s say, four. 

Like a light that cuts through the fog, illuminated before me is a sideways hanging sign: “Sleep Aids.” Yes, my brain tells me, look here. My focus narrows now to scan a single column of jumbled words and logos as I attempt to sift through the chemical rubble that makes up the sleep aid section. “Mel… Mela…” I whisper to myself, not finding what I’m looking for. Use your finger, my brain pipes in. “M… M… M – here it is, Melatonin.” But wait - I see “melatonin” one, two, three, four times… there are at least ten different brands of melatonin, all at different doses. Melatonin gummies at 2.5mg each. Extra strength melatonin quick dissolving tablets at 5mg each. Maximum strength melatonin at a whopping 10mg each. How could they do this to me? My brain adds to the chaos, “Remember that study? Actual melatonin levels in these pills can range from 15% to 400% of what’s listed on the bottle.” A quick Google search reveals that everyone else is as confused as I am. Nearly every brand here is listed as “the best,” certified in this or that regulation process. Looks like I’m going to roll the dice with one of these brands and hope I don’t get the 15% or the 400% mystery pill.

I wonder if this overall confusion about which brand and how much characterizes most people’s experience with melatonin. In neurotherapy, and mental health in general, we talk A LOT about sleep, and when you ask people what their sleep-routine looks like you begin to hear the M word over and over again. In a world that is completely and utterly confused about sleep, melatonin for many, seems like a holistic alternative to a habit-forming sleep aid. I often wonder if people get more of a placebo effect from melatonin than anything, as the hormone is merely an initiator of a brain state where sleep is more likely, rather than a chemical which carries the brain through a deep and restful sleep. That’s not a knock to the placebo, by the way, which has the most powerful and consistent treatment effect in all of medicine… but more on that in my next blog. 

One thing to keep in mind about melatonin is that it is a hormone which is naturally produced and dispersed by the pineal gland in your brain. I think that’s a fact that often gets lost in the conversation about sleep and sleep aids. Hormones are serious business when it comes to the brain and body – if you don’t believe me, ask anyone with a hormone imbalance. This is not to say that melatonin use is inherently dangerous or will surely cause adverse side effects, but I have heard my fair share of reports from people who have overused the supplement and begin to experience depressive symptoms that can be associated with drowsiness. I am not for or against melatonin use in general, but I do want people to understand that when they take it, they are influencing a naturally occurring hormone pathway. If you want to regulate this pathway to work as intended without supplementation, try exposing your eyes to sunlight in the morning and sunlight in the evening. For most, this will give you all the melatonin you need. 

Enough about what melatonin is, let’s talk about what it does. Simply put, melatonin kicks off the possibility for sleep. As Matthew Walker, Ph.D. describes it, if sleep is a race, melatonin is the official who fires the starting shot – not one of the runners. Sometime in the evening, our pineal gland releases a burst of melatonin. The timing of this starting shot is dictated by our circadian rhythm (our internal sleep and wake clock), which is primarily influenced by the time at which the sun rises and sets. So, sometime after sunset – pow. Your suprachiasmatic nucleus (the gear that runs the circadian clock ) tells your pineal gland to release a dose of melatonin and we're off to the races. Melatonin concentration typically peaks around 4:00am, and then decreases again come sunrise.

Now we can see that for most people, we wouldn’t need to artificially start that race – the sun is already doing that for us. There are exceptions for people with circadian disorders, or people who work night shifts, or… you guessed it - people experiencing jet lag. 

When your circadian rhythm is operating in opposition to, rather than in accordance with, the sun, we have a problem. In the jet lag scenario, instead of your greatest potential for sleep coming around 8 or 9pm, it's now showing up at noon. Even worse, your lowest potential for sleep, which normally arrives around 7am, is now arriving when you should be gearing down for sleep. This causes people to become disoriented, groggy, and can lead to poor cognitive and emotional functioning as your internal circadian clock is resetting. For me, I can pretty much count on a headache, lack of motivation, and an overwhelming desire to crawl into bed and watch tv. 

The effectiveness of melatonin for jet lag has been well documented, but if we go back to our original predicament with melatonin of how much we should be taking  – what does the research have to say about that? Here is a brief snippet from a literature review (an analysis of many different research articles) on not only the effectiveness of melatonin for jet lag, but also under which circumstances the hormone supplement was most helpful…

Main results: Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy and patients taking warfarin may come to harm from melatonin.

Reviewer's conclusions: Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It could be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.”


So there you have it – melatonin might not be the best option for your sleep AID, but it seems to be effective at helping people lessen the effect of jet lag. From the review, it sounds like I won’t get much relief as I recently traveled west (Frankfurt to Denver), but next time I go overseas, rest assured I will be taking melatonin at the appropriate times days before, as well as days after, my flight. 

For now – bon voyage, auf wiedersehen, and goodnight. 

I'll see you on the other side of my sleep, hopefully well-rested, readjusted, and ready to talk more about our wonderful and amazing brains. 

John VanDeGrift
Director of Neurotherapy
Aspen Neurofeedback 

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