Melatonin (or Sleepstacy)

Molecule of the month, April 2009

This month the molecule I have been wasting my time thinking about while I should have been doing my PhD is melatonin. The compound is a neurotransmitter which causes us to begin to feel sleepy. It regulates our circadian rhythm: our sleep - wake cycle. In terms of its molecular structure melatonin is a lot like serotonin, the chemical messenger which makes us feel happy. This is interesting in itself - such subtle changes in molecular structure can have huge implications on how a chemical acts on biological systems.

Melatonin and serotonin are very similar in terms of their chemical structure. The hydroxyl and amine groups of serotonin have been methylated and acetylated respectively to give melatonin.

Melatonin and Serotonin are made in the body from the amino acid typtophan. This is an 'essential' amino acid, which means we have to consume it in food - it can't be constructed from simpler molecules in the body. Essential is the word though, since without tryptophan we would be without these two brutes above. So we couldn't sleep and we would never be happy.

The production of melatonin, which takes place in the pineal gland in the brain, is dependant on light. The darker it gets, the more melatonin we begin to produce and the sleepier we begin to feel. Scientists have linked melatonin production levels to the onset of late night activity of adolescents. It appears that around the age of 14 the onset of serious melatonin production begins to become delayed until later in the evening, meaning those crazy kids just don't feel tired at all. Some scientists speculate that this is due to the increased use of screens to play video games, write homework assignments and watch TV during the twilight hours. All that light beaming into childrens eyes, sends the message that it's still bright as day, and there's no need to feel tired yet. Or so runs the theory.

An adolescent brain is a complicated thing, but we can be certain of one thing at least - the Pineal gland is situated near the centre of it

Scientists can’t say for sure though whether teenagers begin to stay up late, and as a consequence their melatonin levels begin to elevate later in the evening, or if the melatonin levels drop off first.

Interestingly, since melatonin production is mainly inhibited by blue light (which has a wavelength of between approximately 450 and 495 nanometres), scientists have had some success in treating insomniacs by instructing them to wear blue tinted sunglasses during the evening. These stop the blue light entering the eyes and trigger the onset of melatonin production.

Disrupted sleeping patterns are a massive source of misery for a significant number of people. 20% of Americans, for example, suffer from sleep disorders. A lack of sleep can lead to what's called secondary sleep disorders, that is social and physical problems resulting from a lack of sleep.

Fortunately Chemists can make melatonin relatively easily, and partly because of that it’s widely available over the counter in the USA as a tempting looking white powder which can purportedly help people with sleep disorders get a decent period of shut-eye. Unfortunately perhaps, it’s not currently legal to sell melatonin in the UK.

Should this be the case? I decided to take matters into my own hands and try to find out if the stuff works.

My self-experimentation was a horrible distortion of the scientific method though. Generally scientists would like to remove external influences and make sure only the variable you want to test (whether of not melatonin has been taken) is changed. It was unfortunate then that me getting hold of some dissolve-under-the-toungue melatonin lozenges coincided with a visit I had to make to the Lake district - one of the most sleep-inducing places in England.

I was pretty nervous about chomping down on this illegal substance so the first night I was in the Lakes I nervously chewed a quarter of a tablet off. My mind did seem to go swimmier than usual before I dropped off, but I could have just been more tired than usual I suppose. The next night I took a whole one. Again I was asleep in no time and didn't wake up until ten the next morning, but I couldn't be sure if this was just becuase I had walked most of the way up a large hill earlier the previous day.

A good scientists should never lose his nerve during an experiment

So unfortunately I had no real evidence whether melatonin worked or not. Since my crude experiments had served only to provide me a few weak anecdotes for my blog, I turned now to the scientific literature for a more robust opinions on melatonin.

A report recently published in the bristish medical journal conducted a careful review of 13 clinical studies of melatonin use in humans which had been reviewed by an independant expert to ensure their validity. After combining the results of the 13 trials the authors found that melatonin doesn't give people significantly more efficient sleep (based on the proportion of time spent actually asleep whilst in bed) or indeed even help people to get to sleep more quickly.

On the other hand though, this doesn't necessarily mean melatonmin wouldn't work for you. The authors found that lots of people did benefit from melatonin - it was just that, equally, lots didn't. While my melatonin source says taking melatonin is, for him 'like switching off a light' this wasn't the case for me. The question is, I suppose, is this just a placebo effect? Who knows, but if melatonin can give my post-doc supervisor (see below) a good nights sleep - sufficient to prevent him from killing me when I use all his glassware at least - then who am I to critcise it?

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Two people have been a massive help to me on this molecule of the month peice, and they're such utter legends that I think a thumbnail sketch is quite in order.

First I turn to Barney Walker, my aforementioned 'grumpy post-doc' (see the about me section). Although I owe Barney quite a debt of gratitude for the fact that he has taught me how to do research chemistry for the last 6 months, I have no qualms when I say he's a morose kind of guy. His mood swings depend mainly on the strength of his morning Starbucks, taken with religious regularity and how well he remembers that he has only 12 weeks to go before moving to the states to be with his girlfriend Gemma. I would also mention that he is large, Scottish and angry. I recently found out that he's one of those people who calls himself by his middle name: real name being Dave. Barney (Dave) supplied me with 'the stuff' for my self experimentation.

Alan Jenners is my second helpmate and is from my church. He contacted me wanting to come and spend a day working in the Davis group research laboratories, so he could find out what it was like being a scientist (for an unrelated project). I refused, on that grounds that he would certainly blow himself up, it's against the rules and it's not a decision I can make anyway. On the upside though, when I suggested he turn researcher for benchtwentyone Jenners jumped at the chance, and when he realised the subject I wanted him to research was melatonin, that was just great - AJ, it turns out, is a sufferer from sleep disorders himself. Illegal sleep drugs to the rescue, Alan?



References

G. E. Bentley, Current Biology, 18, 2008, 736 – 738.

Shipiro et al., J. Clin. Endocrinol. Metab., 5, 2005, 2755 – 2761.

Baker et al., Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis, British medical journal, 2006.