Sleep Hormones and their Effect on the GABA System

May 18, 2023 | Written by Scott Sherr, MD | Reviewed by Marion Hall

Sleep Hormones and their Effect on the GABA System

Sleep allows our bodies to rest and recover, and our brains to process the information we've taken in during the day. But what happens inside our bodies when we sleep? It all starts with the hormones of sleep!

The Importance of Sleep

Before we dive into the hormones of sleep, it's important to understand why sleep is so crucial for our health. In addition to allowing our bodies to rest and recover, sleep is essential for:

  • Brain function: Sleep helps the brain to consolidate and process the information we've taken in during the day, improving memory and cognitive function.
  • Emotional well-being: Adequate sleep has been linked to improved mood and emotional well-being.
  • Physical health: Sleep is essential for the repair and rejuvenation of our bodies, and has been linked to a reduced risk of chronic diseases such as diabetes, heart disease, and obesity.
  • For more information on why we sleep, see our extensive blog article here

Let's now dive into the hormones of sleep (or lack thereof). 


Melatonin is a hormone produced by the pineal gland, located deep in the center of the brain. It helps to regulate our body's internal clock, letting us know when it's time to sleep and when it's time to wake up. Melatonin levels typically rise in the evening, signaling to the body that it's time to start winding down for the night, and fall in the mornings. This is all regulated by something called the suprachiasmatic nucleus in your hypothalamus. For a deep dive into this (and if you are a practitioner), check out the chronobiology module of the essential certification. 

According to a study published in the Journal of Pineal Research, melatonin increases GABA-A receptor activity by binding to the MT1 receptor subtype, which is abundant in the brain and is found in areas responsible for sleep regulation. This study suggested that the use of exogenous melatonin to regulate sleep may be effective due to its ability to increase GABA-A receptor activity.

While melatonin is widely available as a supplement and is generally considered safe, there is some controversy surrounding its use as a sleep aid. One concern is that taking exogenous melatonin can interfere with the body's natural production of the hormone, leading to a dependence on the supplement for sleep. Another concern is that the quality and purity of melatonin supplements can vary widely, making it difficult to know what you're actually taking.

And despite some popular opinions, it has no major effects on sex hormones, including testosterone. 

There are, however, some studies that have suggested that taking melatonin supplements can lead to side effects such as headaches, dizziness, and nausea. It's also possible that melatonin supplements could interact with other medications, so it's important to talk to your doctor before taking any new supplements.

Despite these concerns, many people find melatonin supplements to be an effective way to regulate their sleep-wake cycle and improve their sleep quality.


Serotonin is a neurotransmitter that is often associated with mood regulation and happiness. It also plays a key role in regulating our sleep-wake cycle. Serotonin helps to control the timing and duration of our sleep by signaling to the body when it's time to sleep and when it's time to wake up.

Like melatonin, serotonin also affects the GABA neurotransmitter system. It helps increase the production of GABA, which promotes relaxation and helps reduce stress and anxiety. Boosting your serotonin levels might be a good place to start if you're feeling stressed and having trouble sleeping. 


Cortisol is often referred to as the "stress hormone" because it is released in response to stress. However, it also plays an important role in regulating our sleep-wake cycle. Cortisol levels typically peak in the morning, helping us wake up and feel alert. It then gradually decreases throughout the day, with the lowest levels being reached in the evening, signaling to the body that it's time to start winding down for the night.

However, high levels of cortisol can negatively impact the GABA neurotransmitter system. Cortisol can inhibit the production of GABA, making it difficult to relax and fall asleep. This is why stress and anxiety can often lead to sleep disturbances.

Exercise can help to reduce stress and improve sleep quality, but avoid exercising too close to bedtime, as it can make it harder to fall asleep.

Hormones that Make It Hard to Sleep

While melatonin, serotonin, and cortisol all play a role in regulating our sleep-wake cycle, some hormones can make it harder to sleep. For example, high levels of the hormone ghrelin, which is involved in regulating appetite, can lead to sleep disturbances. Ghrelin is produced in the stomach and signals to the brain that it's time to eat. However, studies have shown that high levels of ghrelin can also make it harder to fall asleep and reduce the quality of our sleep.

Another hormone that can make it hard to sleep is leptin, which is involved in regulating satiety. Leptin signals to the brain that we are full and helps to regulate our appetite. However, low levels of leptin have been linked to poor sleep quality and daytime sleepiness.

Hormones that Wake You Up

While some hormones make it difficult to fall asleep or stay asleep, others can wake you up in the middle of the night. One such hormone is norepinephrine, which is involved in the body's "fight or flight" response. Norepinephrine is released during times of stress or danger and can cause an increase in heart rate and blood pressure. It can also make it difficult to fall or stay asleep, as it can keep the brain alert and vigilant.

Another hormone that can wake you up is cortisol. While cortisol levels are typically lowest in the evening, they can spike in response to stress or anxiety. This can cause feelings of restlessness and make it difficult to fall asleep or stay asleep.

How to Improve Your Sleep Quality

Here are a few tips:

  • Get enough natural light during the day: Exposure to natural light during the day can help regulate your body's internal clock, making it easier to fall asleep at night. 
  • Avoid screens before bedtime: The blue light emitted by screens can interfere with your body's production of melatonin, making it harder to fall asleep. Or at least wear blue blockers and keep the lux of the light low. 
  • Create a relaxing bedtime routine: Taking a warm bath, reading a book, or practicing relaxation techniques like deep breathing can all help promote relaxation and prepare your body for sleep.
  • Exercise regularly: Exercise can help to reduce stress and improve sleep quality, but avoid exercising too close to bedtime, as it can make it harder to fall asleep.
  • Consider cognitive behavioral therapy for insomnia (CBT-I): This is a type of therapy that focuses on changing negative thoughts and beliefs about sleep and can help improve sleep quality.
  • We suggest you consider enhancing GABA tone first and foremost with exercise, meditation, and optimizing GABA production by testing your citric acid cycle intermediates and plasma amino acids, especially for glutamine. Because it is glutamine that converts to GABA in the brain via the enzyme glutamate decarboxylase. Another important note: GABA supplements don't work well because they cannot cross the blood-brain barrier. However, when it is attached to vitamin B3, it can. You can find this type of GABA in Tro Calm


By understanding the science behind the hormones of sleep and their effects on the GABA neurotransmitter system, we can take steps to improve our sleep quality and overall health. So next time you're struggling to fall asleep, remember that it's not just about counting sheep – it's also about understanding the complex interplay between the hormones and neurotransmitters that regulate our sleep-wake cycle. 

And for some help falling asleep if your mind is racing, try Tro Calm. It'll quiet your mind so you can float merrily merrily down the stream.



  • National Sleep Foundation. (2021). Melatonin and Sleep.
  • Fernandez-Mendoza, J. (2020). The role of serotonin in insomnia and sleep disturbances. CNS Spectrums, 25(3), 414-423. doi: 10.1017/S1092852920000837
  • Kalmbach, D. A., Pillai, V., & Roth, T. (2019). The association between cortisol and sleep in adults. Sleep Medicine Clinics, 14(2), 155-165. doi: 10.1016/j.jsmc.2019.01.007
  • Centers for Disease Control and Prevention. (2021). Sleep and Sleep Disorders.
  • Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index. PLOS Medicine, 1(3), e62. doi: 10.1371/journal.pmed.0010062
    • Sánchez-Barceló, E. J., Mediavilla, M. D., & Tan, D. X. (2012). Melatonin and its agonist ramelteon in Alzheimer's disease: Possible therapeutic value. International Journal of Alzheimer's Disease, 2012, 1-11. doi: 10.1155/2012/381974

    Comments (1)

    • So informative. So here I am taking gaba supplements and I find out gaba needs B3 to cross the blood brain barrier – wow, that’s big! Thank you for that! This kind of intelligence is vital!

      Lisa Pruitt

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