Natural Sleep Aids and Medications To Help Improve Your Sleep: Part Three of the Science of Sleep

From the timing and amount of light we are exposed to, when we use electronic devices, and the temperature of our environment, there are so many factors that can influence the quality of sleep we get. My last blog addressed the impact of these factors as well as how you can adjust these things in your life to get more sound sleep. 

However, despite their best efforts and lifestyle modifications, many of my patients continue to have trouble falling asleep, have trouble staying asleep, or suffer from daytime fatigue due to poor sleep quality. This may be because of certain medical conditions or because of imbalances of certain hormones and neurotransmitters within the body such as:

  • Histamine

  • Epinephrine

  • Norepinephrine

  • Serotonin 

  • Cortisol

  • Progesterone

These hormones and neurotransmitters can best be described as messengers within the body. Their purpose is to communicate and deliver signals between the brain and the body. And one of the main signals is the timing and regulation of sleep. 

For patients that suffer from difficulty sleeping due to hormonal and neurotransmitter imbalances, there are many natural sleep aids and sleep medications that can help. But first, we need to review some of the different messengers and how they work to regulate sleep. 

Neurotransmitters That Impact Sleep

Histamine

This first neurotransmitter may sound familiar if you take certain medications for allergies called antihistamines. While histamine is greatly involved in our immune systems, particularly with allergic reactions, it also plays a big role in the sleep-wake cycle. 

Histamine promotes wakefulness by simultaneously activating areas within the brain that make us feel awake and deactivating areas in the brain that cause us to feel tired.¹⋅² 

Throughout the day, histamine levels are expected to be high when we first wake up and be at their lowest before we fall asleep. Some people, however, have high levels of histamine later in the day and may have difficulties falling asleep because of it. 

Patients with high levels of histamine later in the day can benefit from medications called antihistamines. By blocking histamine from communicating with receptors in the brain, patients can expect to get more sound sleep. Three antihistamines I recommend are: 

  1. Diphenhydramine: This antihistamine is the ingredient in over-the-counter medications like Benadryl, Nyquil, and Tylenol PM that causes sleepiness and drowsiness. 

  2. Hydroxyzine: This prescription medication is both an antihistamine and also a mast cell stabilizer. In low doses, it works well to promote sleep, and it’s also used to treat anxiety and panic disorders. 

  3. Ketotifen: This is another prescription medication which is a mast cell stabilizer with mild antihistamine properties. Daily administration of ketotifen has even been found to help with regulation of the sleep cycle.³ You can read more about the mast cell-stabilizing effects of ketotifen in my blog here. 

It’s important to note that while medications like Claritin and Allegra are also antihistamines, they belong to a different subclass of antihistamines that work more on decreasing the allergic response within the body. Therefore, they won’t help with sleep as much as the above medications.

Serotonin 

Serotonin, which is also called 5-HT, is another neurotransmitter that’s known to greatly influence mood and sleep. Many prescription medications for anxiety and depression work on receptors in the brain to allow for more serotonin to be available in the brain. Increased serotonin levels not only improve mood, but they also improve sleep. 

Certain cells in the brain called neurons are in charge of sleep regulation, and they require adequate amounts of serotonin to function properly.⁴

There are certain supplements that have been found to increase serotonin levels in the brain, and sleep can be improved as a result of this. Two supplements that I like to recommend are 5-HTP and L-tryptophan. When you take these supplements, your body turns them into serotonin, which improves sleep regulation and the length of sleep.⁵

Epinephrine and Norepinephrine

Other neurotransmitters related to stress can affect our sleep as well. For example, some people cannot break down epinephrine or norepinephrine very well, which leads to higher than normal amounts of them in their bodies. This keeps the body in a wakeful and even stressful state, and it results in poor, disrupted sleep.  

One of the main pathways in the body that’s responsible for the regulation and metabolism of neurotransmitters such as dopamine, epinephrine, and norepinephrine is the Catechol-O-methyltransferase (COMT) pathway.⁶ Many patients with poor sleep due to high levels of epinephrine and norepinephrine have issues with this pathway. We'll discuss this pathway as well as other pathways related to sleep in next month’s blog.

Prescription Medications To Help With Sleep

Despite lifestyle modification, some of my patients need more help resetting their sleep cycles. This could be due to prolonged disruptions of sleep or certain underlying medical conditions. 

If you’ve been struggling with sleep disruptions for a long amount of time, additional medications may be needed. It’s important to note that these medications help reset the sleep cycle without blocking or influencing the stages of sleep. Here are three that I use often in patients with insomnia: 

  • Trazodone is a medication that belongs to a class of medications called serotonin modulators, and it works by increasing levels of serotonin in the brain. As mentioned before, higher levels of serotonin has been associated with improved sleep. Trazodone was initially used for the treatment of depression, but we now know that it’s a safe and effective treatment for insomnia as well.⁷ 

  • Doxipin is another medication that was originally used for the treatment of depression but is now used for insomnia. It’s a type of tricyclic antidepressant, and it works similarly to trazodone in that it increases the levels of neurotransmitters like serotonin in the brain. When taken in low doses, it’s been shown to improve sleep in those with insomnia.⁸

  • Mirtazapine is also a tricyclic antidepressant, and it also increases levels of serotonin in the brain. It’s also been shown to have antihistamine effects. I like to use this medication in low doses in patients with insomnia and depression because it works well for both conditions.⁹

For patients with long-term sleeping issues, it’s important to have two different protocols for sleep management. I recommend that patients then cycle between their protocols every three days. This helps to ensure that the medications work effectively without leading to dependence of any of the medications. 

If you’re looking to add additional sleep aids to your routine, here are some natural ones I recommend to my patients. 

Natural Supplements to Help With Sleep

Vitamin B5 

Sleep disruption has been linked to deficiencies in vitamin B5 (pantothenic acid).¹⁰ Our bodies use Vitamin B5 to produce a substance called coenzyme A, which is needed for the production of two hormones needed for sleep: melatonin and acetylcholine. Melatonin is the primary sleep hormone that allows us to fall asleep, and acetylcholine is what allows us to enter and stay in the stage of sleep called rapid eye movement (REM) sleep. 

It’s unfortunately difficult for humans to get and absorb vitamin B5 through the foods we eat, so supplementation is often required. When studied in patients with poor sleep and chronic pain, a dose of 100mg of B5 in a B complex vitamin improved sleep within two to three days.¹⁰

Magnesium-L-Threonate

Magnesium supplementation has been shown to help with many conditions like anxiety, constipation, and sleep. However, in order to have a significant impact on sleep, magnesium needs to bind to receptors in the brain. Because of their molecular structure, many magnesium supplements have difficulty getting into receptors in the brain.

Magnesium-L-Threonate is different from other supplements in that it’s chelated, which means that the magnesium is bonded to a different molecule.¹¹ This molecular structure makes it easier for the magnesium to reach the brain and help sleep, as well as cognitive function.¹² 

THC and CBD

Cannabis is made up of two main compounds: tetrahydrocannabinol (THC) and cannabidiol (CBD). While they can both result in feelings of relaxation and calmness, THC and CBD have both been shown to help treat and manage several sleep-related conditions. 

THC has been shown to improve conditions that can negatively impact sleep like obstructive sleep apnea (OSA), post traumatic stress disorder (PTSD), and chronic pain. CBD has been shown to decrease symptoms related to REM sleep disorders as well as daytime sleepiness.¹³ In a large study, CBD improved sleep in 66% of patients.¹⁴

Are You Struggling With Sleep?

If you’re struggling with sleep, know that you’re not alone. With all of the sleep aids available, it can be difficult to find one that works well for you. I find that many of my patients need many different supplements to target the different pathways in their bodies that are disrupted. 

And the neurotransmitters we discussed in this blog aren’t the only things that can affect sleep quality. There are many hormones and underlying medical conditions that can disrupt sleep, and I’ll review these in my next blog. I’ll also be reviewing additional pathways you can support to get better sleep. 

When the right supplements and medications are combined with changes in lifestyle and sleep environment, you can truly experience a good night’s rest.