The Link Between the Endocannabinoid System and Sleep

Alright, we all know sleep is important, but what can we do to help get a better understanding of sleep and how to improve it?

Sleep is regulated by a number of systems in your body and brain, one of them being the endocannabinoid system.

You see, the endocannabinoid system is a bit of a big deal when it comes to your body functions. It has similar cell receptors and endocannabinoids in the brain, immune system, kidney, and gut, but they do different jobs in different places.

A lot of what we know about sleep and the endocannabinoid system come from pre clinical studies, which show important roles of cannabinoid receptors 1 and 2 during different sleep cycles.

Other studies on how the endocannabinoid system works in humans come from treatment with cannabis plants and their cannabinoid compounds found in the flower. Lets delve in to how this system works and how your sleep may benefit from it!

Article Highlight

• The CB1 and CB2 cannabinoid receptors are found in the brain and help regulate the different states of sleep.
• Preliminary research suggests that if you block or inhibit the functions of the endocannabinoid system you can harm your sleep cycles.
• Conversely, in animal models of poor sleep (such as aging), the endocannabinoid system seems to be dysregulated, and levels of endocannabinoids may be altered.
• Multiple clinical trials using cannabinoids and/or the cannabis plant show benefits for people with sleep disturbances, which also support the hypothesis of the critical role of the endocannabinoid system in normal sleep cycles.
• How endocannabinoids, like CBDA (cannabidiolic acid), CBD (cannabidiol), or THC (tetrahydrocannabinol) affect sleep may pave the way for new therapeutic applications.

Jump to

• The Importance of sleep
• The Endocannabinoid System and Sleep
• What to do with Your Sleep, Cannabis, and the Endocannabinoid System
• Conclusion

The Importance of Sleep

If you’ve every listened to trainers who work with professional athletes, they will tell you sleep is recovery, and is 50% responsible for how you play.

You can exercise and diet right, but its when you sleep, thats your body takes those inputs and actually uses them for restoration and growth.

No sleep, no bueno, thanks for playing.

What sleep architecture looks like

Sleep can be complicated, but its important to break it down into its main components:

1. Light Sleep (aka N1, Non-REM): Occurs throughout the night between the deep sleep and REM cycles. During this phase, the body is not as regenerative as the deep sleep cycles.
2. Deep sleep (aka N2, Non-REM): Important for memory and brain plasticity, occurs more frequently earlier in the sleep window.
3. Deepest Sleep (aka N3, Non-REM): This cycle is for tissue, bone, muscle regrowth and immune system maintenance. Occurs earlier in the sleep window.
4. REM (rapid eye movement): Brain is active during this period, and occurs the most towards the end of the sleep window in the morning. This is when you dream.

While these are the basic profiles of the different sleep patterns, most sleep tracking apps will break it down into light sleep, deep sleep and REM sleep, so you can how you did the night before.

What poor sleep may look like

Poor sleep is when you feel fatigued, low energy and groggy in the morning, and most people are probably getting poor sleep.

So whats causing poor sleep? Many things can, so here are some of the top culprits to look for:

• Alcohol consumption in the evening: 1 or more drinks, depending on the person, can decrease the time spent in critical deep sleep cycles. Even if you go to bed at 9 and wake up at 6, you can still be fatigued if you drank the night before due to poor deep sleep cycle time and thus no regeneration.
• Stress and Anxiety keep you up: excessive stress and anxiety can make it very difficult to turn off your brain and fall asleep. This means that while you go to bed at 10, you dont fall asleep until 11:30 or even 12. Can I just sleep in more? Well not really, our body has a natural rhythm, called a circadian rhythm, that regulates when we get deep sleep, REM and light sleep. If we push our sleep time too late into the night or wake up too early, it cuts short our deep sleep cycle or REM cycle time.
• Sleep apnea: this can come from obesity, chronic rhinitis, and leads to low oxygen levels in the blood. In turn, this causes your body to momentarily wake up to breath better and take in more air.
• Stimulants: this is a big topic, but caffeine and nicotine are the most common compounds that affect sleep. Caffeine has a half of around 5-6 hours while nicotine is only around 2 hours. Thus, your timing of when you consume these relative to when you go to bed is critical to the quality of sleep you get. Drinking a cup of coffee at 12 noon, is like drinking a half cup at 6pm and a quarter cup at midnight. Its important to remember that this is an average, some people may be fine drinking coffee at 7pm, but others could be a slow metabolizer and shouldn’t drink after 10am!

If you interested in improving sleep, we recommend tracking it with something like an Oura ring or a whoop. A good biometric will have much better understanding of your sleep cycles, and you can track any interventions that you do.

 

The Endocannabinoid System and Sleep

Alright friends, it’s time we chat about that deep connection between the cannabis plant, the endocannabinoid system, and good ol’ sleep quality.

The sleep quality is largely an interplay between different parts of the brain, and the endocannabinoid system appears to have an important role in regulating sleep quality and cycles.

The endocannabinoid system is found throughout the body, in different organs, immune cells etc, but for this topic we are focusing on their role in the central nervous system.

What are the components of the endocannabinoid system

The endocannabinoid system consists of three main components:

1. The receptors: the endocannabinoid receptors are varied, but the two main ones are CB1 and CB2 receptors. There is also an interplay between endocannabinoids and serotonin receptors, such as 5HT1A.
2. The endocannabinoids: there are two main endocannabinoids that bind the cannabinoid receptors, ANA (anandamide) and 2-AG (2-arachidonylglycerol).
3. The enzymes: a number of critical enzymes are involved in the production of the endocannabinoids that control the activity of the receptors, such as FAAH (fatty acid hydrolase).

While these are not the only parts of the endocannabinoid system, they are certainly some of the main ones that are well studied.

Pre clinical trials on endocannabinoids and sleep

Many sleep studies start with pre clinical trials where the biology of how sleep is regulated gets worked out. This can involve gene changes and drug administration while monitoring changes in brain waves and sleep cycles.

• Inhibition of CB1 receptors in the brain causes an increase in wakefulness and prevents the onset of sleep.
• Injection of ANA (the natural endocannabinoid that binds CB1 receptors) led to a decrease in wakefulness and an improvement in deep sleep type cycles.
• Inhibiting the enzymatic breakdown of endogenous cannabinoids (anandamide) improved working memory in mice exposed to stress. In untreated mice, stress impaired memory, increased stress hormones and negatively effected circadian rhythms.
• Treating non-human primates with THC increase night-time activity and showed decreased sleep quality. However, the doses of THC were high (think 70mg dose for a 150lb person), and given daily, so care should be taken when interpreting these results.

Pre clinical trials are varied in their results, but we can draw 2 conclusions from the current data:

1. The endogenous cannabinoids and the endocannabinoid system are important for quality sleep.
2. We do not have enough studies on how cannabinoids may be impacting various sleep cycles.

Human sleep trials with cannabis plant extracts

Cannabinoids are often by many people for help with improving sleep, but robust clinical trials with important defined endpoints are difficult to perform and fund, and thus there is not robust data in this area.

However, we do have results from smaller studies that may help highlight where we are at:

• In 11 patients with no history of marijuana use, cannabis use was tracked for 3 months to test memory and sleep changes. Patients were tested before and after the 3 months. Memory tests showed moderate improvement, and patients reported slightly better sleep quality. Complications of the study are low number of participants, self reporting, no defined endpoints, and no consistent dosage.
• To test if CBD has an effect on sleep cycles, healthy 27 patients were recruited in a crossover trial. 300mg CBD gel cap or placebo was given prior to a sleep study, and following day the conditions were switched. CBD showed no negative effects, or changes, on the normal sleep cycles.
• In a study with 8 healthy participants, treatments with THC (15mg) or THC+CBD (5mg + 5mg or 15mg + 15mg) was performed in a sleep study clinical setting. No changes in sleep architecture picked up on the electroencephalogram was found with THC 15mg, but the THC + CBD at 15mg each showed a modest decrease in stage 3 sleep and more wakefullness. However, testing the following day showed THC at 15mg induced general grogginess and decreased memory performance, not found when combined with CBD at the 5mg dose range. Overall, CBD interacts with THC to increase wakefullness at higher concentrations, and THC should probably be titrated to lower amounts if taken for sleep.
• A clinical trial from a cannabis company using a formulation of 10mg THC/1mg CBN/0.5mg CBD found some sleep benefits for patients with diagnosed insomnia. While the sample size was low, 24, it is one of the better controlled studies for sleep analysis and benefits.

The various effects of the cannabis plant on sleep seem to be mixed, and depend on the dosage, timing, and acute vs chronic use of cannabinoids.

For example, you can see the figure below on how use of different cannabinoids affects the sleep cycles through the endocannabinoid system:

 

Now, keep in mind, scientific research on all of this is like a beautiful symphony in progress—there’s still a lot to learn. While clinical trials are helping us have a better understanding of how these sleep-enchanting compositions play out between the cannabis plant, endocannabinoid system, and human health, more research is needed to iron out the finer details.

 

What to do with Your Sleep, Cannabis, and the Endocannabinoid System

Sleep is critical to overall health, and poor sleep is associated with almost every known disease from cancer, to cardiovascular and neurodegenerative.

So now that you know a little about the endogenous cannabinoid system and its role in sleep, what can you do with that?

Is your sleep hygiene already good?

While the right cannabinoids may help get you some extra Zzzz’s, lets take a quick look at where your foundation is before adding on top:

1. Are you exercising in the morning or during the day at least 3 days a week? Exercise in any form drastically improves your probability of getting better sleep. If this is not in your routine, dont bother with supplements or drugs.
2. Are you consuming stimulants late into the day? Cut out the caffeine after 12 as a general rule. It can be found in many beverages, and is in tea as well, so make sure your not consuming late into the day.
3. Alcohol consumption in the evening can really impact your sleep. For many people they are so used to have a couple beers or drinks when they get home, and have never tried to have none. Get an Oura ring or Whoop that directly measures your heart rate and heart rate variability, and then test out drinking vs not.
4. Blue light from screens before bed is a significant problem for many! Blue light inhibits your body from making melatonin in the brain, thus drastically reducing your ability to sleep. Make sure to stop screen watching at least 1 hour before bed. You can also use blue light blockers or many phones also have a night option you can turn on.

While not an exhaustive list, this should cover the majority of issues people have with getting quality sleep.

Cannabinoids for sleep

While the scientific research suggests that cannabinoids and the endogenous cannabinoid system are certainly important and can affect sleep, how do we best navigate this based on the current research?

• CBD on its own does not appear to affect sleep architecture, which is good since you dont want something that can negatively effect your baseline sleep. Combining CBD with higher doses of THC may lead to poorer sleep, but whether this is just a THC response for a synergy effect remains to be seen.
• THC on its own may not be good for long term sleep quality, however, this is most likely a dose response problem as well. Since studies show that higher doses of THC (15mg and above) can decrease sleep quality, there may be therapeutic applications at low doses.
• CBN (cannabionol) is often touted as a “sleep cannabinoid”, but there is limited research on its application, so we just dont have that much to go for its efficacy.

Depending on the reasons why you are getting poor sleep, cannabinoids may or may not be a great option for you. For example, if your sleep problems come from stress and anxiety, its possible that CBD/CBDA oil may help, even in combination with a low dose THC.

If your sleep problems are due to sleep apnea, or drinking later in the day, cannabinoids may not be able to help.

Choosing the right CBD or THC for sleep

There are many hemp products on the market, so it can be a bit confusing on what to choose.

Stress, Anxiety and Sleep products

If you are high anxiety and stress, you may benefits from CBD or its parent compound CBDA (cannabidiolic acid). Both forms are found to help with stress and anxiety in pre clinical trials, and many customers are using them for relaxation.

CBDA is the natural precursor to CBD, and is what the cannabis plant actually makes. In fact, CBDA is over 500% better absorbed than CBD, making it one of the most potent cannabinoids on the market.

If taking CBD or CBDA for sleep, make sure to take it around 2 hours before bedtime. This give it enough time to calm the mind, and any wakefullness effects can be mitigated.

Using THC products for sleep

Many of the popular hemp products on the market for sleep contain THC, either delta-9 or delta-8. While it has psychoactive properties, you need to be careful with the dosing. Recently, delta-8 THC has become popular for sleep because it does not get you as high as delta-9 THC.

Based on the reported studies, a low dose range appears to have limited negative effects on the sleep cycle. A low dose can range from 1mg to 5mg, and will vary based on the individual.

Combination CBDA, CBDA and THC products for sleep

Combination products that have THC and other non psychoactive cannabinoids are popular, in part due to the relaxing nature of the synergy between the THC and CBD or CBDA.

When choosing a product, make sure to keep the delta-9 THC low (1-5mg range), and if delta-8 it can be a bit higher (5mg to 10mg) because its not as potent.

If you are not comfortable with the effects of THC, you can try and high CBD/CBDA product with lower amounts of THC.

Remember to start with a low amount and work your way up if you are new.

Always check for a CoA

All good hemp products should be tested by a third party testing lab, and come with a report (certificate of analysis; CoA) that shows the testing done and the results.

The results should have the potency (amount of cannabinoids), and test for the presence of unwanted contaminants of heavy metals, pesticides, solvents, and microbials.

 

Conclusion

Well, my fellow sleepyheads, it’s time to wrap up our cozy chat about the endocannabinoid system, sleep, and our new BFFs, CBD and CBDA. Who would have thought that our bodies have a built-in pharmaceutical company, right?

It’s amazing how these cannabinoids interact with our body—especially CB1 receptors—to help us combat various health problems. What’s even more remarkable is that, unlike THC, both CBD and CBDA don’t get us high, yet still cloak us with potential health benefits like a warm, cozy blanket.

Finding the right dose and mixture of cannabinoids that work for you will take some trial and error, and we highly recommend tracking your sleep.

While more research is always wanted, it can be slow when there is not a pharmaceutical company paying for the work. So I would not hold your breath on this one.

 

–Team Dos