Melatonin

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​


"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.

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."

"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."
 
Long-term melatonin use linked to 90% higher heart failure risk

Long-term melatonin use was linked to a striking increase in heart failure risk, challenging assumptions that the popular sleep aid is harmless.

Date :August 29, 2026

Source: American Heart Association

Summary: People with chronic insomnia who used melatonin long term had a roughly 90% higher risk of developing heart failure over five years, according to a large preliminary study. The findings do not prove melatonin causes heart problems, but they raise new questions about the safety of taking the popular sleep supplement for extended periods.

What the Study Included

  • The analysis included 130,828 adults (average age of 55.7 years; 61.4% women) who had been diagnosed with insomnia.
  • The data came from TriNetX, established in 2013, a growing global network of real-world, de-identified patient information used for medical research.
  • Of the participants, 65,414 had been prescribed melatonin at least once and reported using it for at least one year.
  • Researchers also created a comparison group (control group) made up of people who had never been prescribed melatonin. These participants were matched to the melatonin group using 40 factors, including demographic characteristics, existing health conditions, and medications.
  • Anyone who had already been diagnosed with heart failure was excluded, as were people who had been prescribed other kinds of sleeping pills such as benzodiazepines.
  • The melatonin and comparison groups were matched for age, sex, race/ethnicity, heart and nervous system diseases, medications for heart and nervous system diseases, blood pressure, and body mass index.
  • Researchers then examined electronic medical records covering the five years after the groups were matched.
  • For the primary analysis, they searched for medical codes indicating an initial diagnosis of heart failure. Secondary outcomes included codes associated with hospitalization for heart failure or death.
  • The researchers also carried out what is known as a sensitivity analysis, a method used to check whether results remain similar when the study criteria are changed slightly.
  • For this additional test, participants in the melatonin group had to have filled at least two melatonin prescriptions at least 90 days apart. The association with higher heart failure risk remained, providing an additional check on the original findings.
  • Even so, the researchers emphasize that the study was observational. It identified an association between long-term documented melatonin use and serious health outcomes, but it cannot establish that melatonin directly caused those outcomes. Further research will be needed to determine whether long-term melatonin use itself affects cardiovascular health and, if so, why.
 
Mij said:
Long-term melatonin use linked to 90% higher heart failure risk

Long-term melatonin use was linked to a striking increase in heart failure risk, challenging assumptions that the popular sleep aid is harmless.

Date :August 29, 2026

Source: American Heart Association
Click to expand...
Seems to be in reference to the findings discussed in the following thread (note there are some potential issues here, particularly with patient selection):

https://s4me.info/threads/long-term...ve-negative-health-effects.47119/#post-654044
 
The people using melatonin in the USA, where no prescription is required, were presumably suffering from self-diagnosed insomnia. I don't believe they would buy and take melatonin if they didn't need it, but perhaps I'm naive.

In the UK, where melatonin is not available over the counter, although it used to be several (15??) years ago, people with insomnia are essentially expected to just tough it out and put up with it, or at least that has been my experience. I developed insomnia when I was 9, and had it all my life until very recently, over 50 years later.

I wonder what effect nearly 60 years of insomnia has on my risk of heart disease and heart failure. The medical profession and the NHS doesn't have anything that helps long term to help people sleep in my experience.

I remember quite a few years ago trying diphenhydramine for a few months which was available over the counter. It helped me slightly and temporarily in falling asleep. I gave it up when I read that it increased the risk of dementia which is something I'm terrified of.

The things I've found actually helpful are magnesium tablets, and having my hypothyroidism treated. It only took me 60+ years to find that magnesium helped and 50+ years to discover that better levels of thyroid hormones helped slightly. I found out about magnesium myself. And also have to treat my own thyroid hormone levels.
 
Mij said:
Long-term melatonin use linked to 90% higher heart failure risk

Long-term melatonin use was linked to a striking increase in heart failure risk, challenging assumptions that the popular sleep aid is harmless.

Date :August 29, 2026

Source: American Heart Association

Summary: People with chronic insomnia who used melatonin long term had a roughly 90% higher risk of developing heart failure over five years, according to a large preliminary study. The findings do not prove melatonin causes heart problems, but they raise new questions about the safety of taking the popular sleep supplement for extended periods.

What the Study Included

  • The analysis included 130,828 adults (average age of 55.7 years; 61.4% women) who had been diagnosed with insomnia.
  • The data came from TriNetX, established in 2013, a growing global network of real-world, de-identified patient information used for medical research.
  • Of the participants, 65,414 had been prescribed melatonin at least once and reported using it for at least one year.
  • Researchers also created a comparison group (control group) made up of people who had never been prescribed melatonin. These participants were matched to the melatonin group using 40 factors, including demographic characteristics, existing health conditions, and medications.
  • Anyone who had already been diagnosed with heart failure was excluded, as were people who had been prescribed other kinds of sleeping pills such as benzodiazepines.
  • The melatonin and comparison groups were matched for age, sex, race/ethnicity, heart and nervous system diseases, medications for heart and nervous system diseases, blood pressure, and body mass index.
  • Researchers then examined electronic medical records covering the five years after the groups were matched.
  • For the primary analysis, they searched for medical codes indicating an initial diagnosis of heart failure. Secondary outcomes included codes associated with hospitalization for heart failure or death.
  • The researchers also carried out what is known as a sensitivity analysis, a method used to check whether results remain similar when the study criteria are changed slightly.
  • For this additional test, participants in the melatonin group had to have filled at least two melatonin prescriptions at least 90 days apart. The association with higher heart failure risk remained, providing an additional check on the original findings.
  • Even so, the researchers emphasize that the study was observational. It identified an association between long-term documented melatonin use and serious health outcomes, but it cannot establish that melatonin directly caused those outcomes. Further research will be needed to determine whether long-term melatonin use itself affects cardiovascular health and, if so, why.
Click to expand...


this is a problem here:

Mij said:
  • Of the participants, 65,414 had been prescribed melatonin at least once and reported using it for at least one year.
  • Researchers also created a comparison group (control group) made up of people who had never been prescribed melatonin.
Click to expand...

So they are compared 'people who were prescribed melatonin with those who weren't prescribed melatonin' - they didn't have to have taken it

and NOT (as the title inferred) 'people who took melatonin long term with those (ideally with similar conditions) who didn't'

taking melatonin ONCE isn't long-term. neither is a year.

Importantly ... to be prescribed melatonin vs not be prescribed melatonin being the difference, then which actual criteria does that tick? I'm assuming being ill enough to ask and being ill enough for an HCP to sign it off


I have to wonder about conflicts of interest here if your research question/title is going to be about 'long term effects of melatonin' and then your actual criteria are that?
 
I've read studies that melatonin as an antioxidant has therapeutic properties that may contribute to its cardioprotective effects.

I tried very low dose melatonin for sleep but it didn't work for me, I might have continued taking it for its antioxidant effects, but didn't because it made me feel not so good.
 
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