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The Many Modulators of Sleep

As we go through our lives, we spend a third of that time sleeping. Although this time does not amass to anything consciously productive, it is a crucial time for the proper recovery and relaxation of our bodies. Without sleep, we spend our waking hours in a state where our productivity is less than optimal (no matter what a college student cramming for an exam would tell you).

This blog looks at some of the factors that can affect this crucial period of our lives and how it can be positively or negatively modulated.

How Do We Define Sleep?

If you ever wore a fitness watch with sleep tracking capabilities to bed, you may see something akin to the graph below.

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Your body cycles between four different categories of sleep: Awake, Light (stages 1 and 2), Deep (stage 3), and REM (or Rapid Eye Movement). During REM sleep, which happens multiple times at night, we tend to dream.

Most sleep trackers will give you the time you slept, and even analyze if your sleep was good or not. However, the ultimate judge of this activity is our attentiveness and energy the next day.

Alcohol and Acute Insomnia

Insomnia is simply the inability to fall or to stay asleep. As some of us may know from prior experience (again most likely in college), drinking too much alcohol can have a sedative effect. So if acute insomnia hits, we may be tempted to get that nice old bourbon out with the hope that a glass would make us fall asleep faster. This is partly true – but there is a caveat.
Young woman savoring the bouquet of a glass of wine as she sniffs at the glass with her eyes closed in bliss as she concentrates on the smell with copyspace indoors in the kitchen Your sleep stages may be disrupted depending on what time you drink. Alcohol can make us fall to sleep faster, even taking us to stage 3, but at the detriment of REM sleep.

Once the alcohol starts to wear off, we end up with an increase in REM sleep (also known as REM rebound). Although dreaming is very subjective, it has been reported in some circles that dreams after consuming a lot of alcohol can be “interesting”.

So What is Happening at the Molecular Level?

Alcohol, as well as various prescribed sleeping pills such as Valium, Xanax, Ambien, and Lunesta, act on a very crucial ion channels in the brain known as gamma-aminobutyric acid receptors (GABA Receptors).

These receptors act as the primary inhibitory mechanism in nervous system. When activated by the neurotransmitter GABA, they act by “relaxing the nerves,” allowing the body to fall asleep. Sedatives such as alcohol and sleeping pills enhance the activity of GABA receptors, facilitating entry into sleep.

However, these sedatives can also be habit-forming. This is well attributed to alcohol and benzodiazepine-based drugs such as Valium and Xanax, which have several other side effects beyond the scope of this blog.

Modulation of the GABA Receptors

When a drug enhances the effect of a receptor, it is acting as a positive modulator. Alcohol and most sedatives fall into this class, but so do simple aromatics such as lavender.

Lavender essential oil contains a fragrance component called linalool, which likely acts on the GABA receptors by mildly enhancing their activity. Because of this, lavender can also slightly affect our REM sleep. Anything that positively enhances your GABA receptors can make you relaxed and eventually groggy.

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Over-activation of GABA Receptors

Sometimes too much of a good thing is a bad thing. Idiopathic hypersomnia is a disease that causes excessive daytime sleepiness even after a good night sleep. Patients feel that sleep is not restoring their levels of attentiveness, and report that they feel as if they are “in a fog.” They may have great difficulty waking up from sleep or naps, feeling that their sleep was not productive to their wellbeing.

A recent study demonstrated that some cases of idiopathic hypersomnia can be due to the existence of an increased positive modulator acting upon GABA receptors. This was proven by applying cerebrospinal fluid (CSF) from patients to cells expressing the GABA receptors. When the receptors were subjected to CSF, a marked increase in their activity was observed. The link to the study is below:

Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABA(A) receptors

Dr. Andrew Jenkins recently demonstrated this research using an automated patch system, IonFlux Mercury HT. You can view his webinar below:

The Bottom Line

Sleep is a complex and necessary state in our lives that is vastly misunderstood. Although taken for granted, its disruption (whether insomnia or hypersomnia) can affect our wellbeing and decrease our quality of life. When our sleep is affected, we may inadvertently reach for a common sedative like alcohol to aid in sleeping. Sometimes these sedatives are mild and all around us (e.g., lavender). In either case, consciously or unconsciously, we all value the quality of our sleep.

Ali Yehia
Ali Yehia, Ph.D.

Ali Yehia has a Ph.D. in Cardiac Electrophysiology from McGill University. He has been involved in ion channel screening using Automate Patch Clamp since 2006. He joined Fluxion Biosciences in 2012, where he developed ion channel assays and IonFlux Mercury systems. He was the Chief Scientific Officer at Fluxion before moving to Cell Microsystems as the new Senior Director of the IonFlux product.

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