Beyond sleep aid: How melatonin research could transform sleep and pain therapies
Pre-clinical studies show that targeting specific melatonin receptors—proteins activated by melatonin in the brain—may lead to promising treatments for sleep disorders and chronic pain

A good night’s sleep is essential for overall health and well-being, but for many people, it remains out of reach. An estimated 10–15% of Canadians experience symptoms of insomnia that affect daily lives, and up to 10% could be living with a sleep disorder. Beyond its impact on health, insomnia costs approximately $5,010 per person per year.

When sleep problems arise, many people turn to melatonin supplements, which mimic the body’s naturally occurring sleep hormone, but their effects are modest. Neuroscientists like Dr. Gabriella Gobbi at McGill University are now uncovering that melatonin acts through a complex system in the brain.

At the center of this complex system are two receptors known as MT1 and MT2. Think of them as “locks” that melatonin, the “key”, binds to in order to affect sleep. “Sleep depends on where and how these two melatonin receptors are activated,” Dr. Gobbi explains.

While researchers have long known about MT1 and MT2, their distinct functions are still being studied. In a review of existing evidence, Dr. Gobbi helps clarify how each receptor may impact different stages of sleep. MT1 receptors may regulate the stage of sleep during which we dream, also known as REM sleep, whereas MT2 is associated with deeper non-REM sleep, which is essential for brain recovery and restoration.

Dr. Gobbi’s work also shows that activating these receptors individually could optimize specific sleep stages. What happens when both receptors are activated at once? The benefits may cancel out, Dr. Gobbi explains, highlighting the importance of selectively targeting a single receptor.

Her team also developed experimental drugs designed to selectively activate either MT1 or MT2 receptors. A study in animal models showed that an MT1-targeting compound activated specific brain regions resulting in increased REM sleep.

Dr. Gobbi’s insights may help explain why melatonin supplements may be ineffective at maintaining sleep throughout the night: “Melatonin supplements are not designed to selectively activate specific receptors,” she says. “This is why it’s essential to develop targeted therapies.”

In addition, her research is uncovering a potential role for melatonin MT2 receptors in managing chronic pain beyond its role in deep sleep. Another study showed that a medication targeting MT2 receptors could help reduce nerve pain by switching on our brain’s natural opioid system—a circuit of neurons involved in pain regulation.

These insights point to a promising alternative to traditional opioids, potentially with fewer side effects and lower risk of dependence.

“CIHR funding enabled us to turn a molecule that began as a concept on paper into a real drug candidate—one that has the potential to open the door to a new class of treatments for sleep disorders and pain.” Dr. Gobbi says.

Her team has already patented several compounds that selectively target melatonin receptors and is working to bring them into clinical trials. Looking ahead, Dr. Gobbi is also exploring how MT2-targeting therapies could be applied to conditions such as autism spectrum disorder.

At a glance

Issue

Sleep disorders and chronic pain affect a significant portion of the population, with an impact on health and economic burden. Common sleep treatments like melatonin supplements do not work consistently for everyone. Opioid medications, often prescribed for nerve pain, can carry significant risks of dependence and risk of death.

Research

Dr. Gabriella Gobbi’s work is reshaping how researchers understand melatonin and its receptors—not just as a sleep aid, but as key players in brain function with broad therapeutic potential for sleep disorders and chronic pain.