Can you build tolerance to melatonin?
The concept of tolerance describes a state when you stop responding to a specific molecule, or drug. When you develop a tolerance to a medication, you require a higher dose to achieve the same effect as before.
Current research has no definitive results on whether you can develop tolerance to melatonin. Some experiments indicate that humans can develop a tolerance to melatonin, while others show the opposite.
On one hand, some researchers found that the effect of melatonin on sleep is not achievable already on the second day of use [1].
Other scientists found similar results but noted that the tolerance developed after weeks of use [2].
On the other hand, other articles indicate that scientists have found no evidence of tolerance to melatonin in humans [3, 4].
The very different results show that more research is required to understand the topic of melatonin tolerance.
Additionally, subjective factors have to be considered when considering tolerance to a substance. For example, the genetic variant of the MTNR1B gene and metabolic rate play important roles in how an individual responds to melatonin [2, 5].
What is melatonin?
Melatonin is a natural hormone that regulates the circadian rhythm, an internal clock of sleep and awareness [6].
The chemical description for melatonin is N-acetyl-5-methoxy tryptamine [6].
The primary side of melatonin production is the pineal gland in the brain [7].
Naturally, melatonin levels increase during the night, simulated by darkness, and decrease during the day [6]. This is one reason why melatonin is called the hormone of darkness [8, 9].
Melatonin can also be supplemented in addition to being produced physiologically. It is commonly used for sleep disorders like insomnia [10].
Melatonin also has other functions in the body. For instance, it is a potent antioxidant and influences the cell cycle [6, 8].
What are the uses of melatonin?
You can take melatonin for
- jet lags [11],
- shift worker [11],
- blind people with circadian rhythm disturbance [11],
- insomnia [12],
Potential uses of melatonin include anti-inflammatory treatment for bacterial and viral infections [13], contraceptives [12], anti-cancer therapy [14], and neurodegenerative disease therapy, like Alzheimer’s [7].
However, these uses need more research and FDA approval.
What are alternatives to melatonin?
Several alternatives as substitutions for melatonin exist.
For example, you can take ramelteon and tasimelteon instead of melatonin. These drugs are melatonin receptor agonists. They have a similar effect on sleeping and are FFDA-approved for insomnia treatment [15, 16].
In Chinese medicine, (-)-epigallocatechin-3-gallate (EGCG) and lavender oil are used as melatonin substitutes [17].
Also, valerian, an herbal supplement, has shown effectiveness in sleep disorders therapy [18].
However, even though many alternatives are on the market, not all may work for everyone. Before trying any alternatives to melatonin, you should consult your doctor to find the best possible fit for you.
What are the side effects of melatonin?
The most common side effect of melatonin is daytime sleepiness [20].
Other possible side effects of melatonin are
- headaches [21],
- dizziness [20],
- nausea [22],
- depression [20],
- shaking hands [20],
- anxiety [20],
- abdominal cramps [22],
- irritability [20],
- confusion [20],
- low blood pressure [22].
- mild decrease of body temperature [20],
In children with neurological disorders, melatonin can cause bedwetting. Also, such children, when taking melatonin, are at a higher risk for seizures [23].