Melatonin: a potential solution to make those hours in bed count

McGill scientists discover a novel compound that can selectively promote deep restorative sleep

We have all had a few terrible nights with barely any sleep. For students, dark circles, bags under the eyes, and increased heart rates are most prominent around exam period. Luckily, this transient insomnia soon comes to an end once we face the fate that awaits us in the exam room. Unfortunately, approximately 10 per cent of Canadians suffer from a different type of sleeplessness, chronic insomnia, a condition that can span from six months to years.

Since the definition of insomnia can be vague, the American Sleep Association has clarified the condition as being both a sleeping problem and an impairment of daytime activities. To alleviate the detrimental effects of insomnia, a handful of drugs – such as benzodiazepine and derivatives – are available on the market. Some, however, prefer a more natural solution.

A recent study led by Dr. Gabriella Gobbi and colleagues at the McGill University Health Centre (MUHC) established a new understanding of the neurohormone melatonin, and outlined a compound named UCM 765 that may enhance the quality of sleep.

It is crucial to know that sleep is an active cycle, which is largely divided into Rapid Eye Movement Sleep (REMS) and Non-Rapid Eye Movement Sleep (NREMS) sometimes referred to as Slow-Wave Sleep (SWS). SWS is known as “restorative sleep” or “deep sleep.” The average adult undergoes four to five sleep cycles per night, and spends 15 to 20 per cent of the total sleep time in deep sleep. This stage of sleep is critical to our well-being, because it allows the growth and repair of tissues and the restoration of energy as well as memory consolidation.

Although controversy surrounds the claim that melatonin induces sleep, this neurohormone has been proven to control a structure in the brain’s hypothalamus called suprachiasmatic nucleus, which is involved in the circadian rhythm, a part of our sleep cycle. Melatonin binds to two receptors, MT1 and MT2, and it is the latter which interacts with UCM765. Dr. Stefano Comai, a member of Dr. Gobbi’s team, has studied this receptor.

Since her lab focused on depression and anxiety disorders, it came as a surprise when they found that UCM 765 induces sleep in rats and mice. After an injection of the compound into the blood stream, the rats showed a selective increase in the NREMS without affecting the REMS. It was discovered that the brain area involved in sleep regulation became more activated when the compound interacted with the MT2 receptors. Results were validated in mice lacking either type of receptors – mice with no MT1 receptors slept more when the compound was administered, whereas mice with no MT2 receptors had no change in sleep following the injection.

Although numerous sleep-inducing drugs – like benzodiazapenes – are available, many of them have adverse side effects, such as drowsiness, cognitive impairment, dependence, and tolerance to the drug after a lengthy treatment. These drugs can also alter phases of REMS and NREMS thereby changing the sleep architecture. UCM765 seems particularly promising as it induces NREMS without disrupting the sleep cycle. The compound has to undergo a series of clinical trials in humans before entering the market. However, Dr. Comai expects that the new drug will be tremendously efficient in treating insomnia by specifically targeting restorative sleep.