CBD (cannabidiol) is commonly used to treat sleep symptoms like insomnia. Learn more about cannabinoids, how CBD works, its forms & effects on the body. Wondering how to determine the best CBD dosage for sleep? Check out our blog to discover how much CBD to take before dozing off into dreamland. CBD Oil Dosage For Sleep There isn’t one dosage that will work for everyone, but there are general guidelines. T he U.S. Food and Drug Administration doesn’t have recommendations on how much to
CBD Oil Dosage For Sleep
In recent years, the use of marijuana and CBD for the treatment of a variety of conditions has risen significantly. Specifically, CBD has been found to have potential health benefits for symptoms like insomnia. Here’s a little background on what CBD is and how it impacts your sleep and body.
What Are Cannabinoids and CBD?
Cannabinoids are chemical compounds that bind or attach to certain receptors in the central nervous system and act as chemical messengers. Depending on the specific cannabinoid, it may have varied effects on the body.
The most well-known and probably most researched cannabinoids include cannabidiol (CBD) and tetrahydrocannabinol (THC). We know that THC is the cannabinoid that leads to the “buzz or high” from cannabis use.
CBD differs from THC and does not cause psychoactive effects or a “high.” Because it does not cause the psychoactive effects and it might help certain conditions, such as pain, anxiety, and insomnia, CBD is gaining traction as a possible treatment for several diseases.
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How Do CBD and Cannabinoids Work?
Not everything is completely understood about how cannabinoids (including CBD) work. What we do know from research is that CBD and cannabinoids interact with proteins and cells in the brain. A relatively newly discovered system may also hold some answers.
The Endocannabinoid System and Sleep
Researchers discovered that the endocannabinoid system plays a role in maintaining certain body functions, such as mood, appetite, sleep, and regulating circadian rhythms. Within the endocannabinoid system is a network of cannabinoid receptors in the brain and central nervous system.The two primary receptors identified are CB1 and CB2.
Cannabinoids attach to these cells and have various effects. As far as how they may affect sleep, some research indicates that the cannabinoid CBD may interact with specific receptors, potentially affecting the sleep/wake cycle.
Additionally, CBD may also decrease anxiety and pain, which can both interfere with restful sleep. By reducing certain symptoms, it’s also possible that sleep may improve.
What Does the Research Say About CBD?
Although more studies need to be performed, some research supports the theory that CBD and cannabinoids may improve sleep. This study published in the journal, Medicines, involved 409 people with insomnia. Data was collected from June 2016 to May 2018. Participants rated their symptoms of insomnia on a scale of 1 to 10 with 10 being the most severe. Starting symptoms were rated 6.6 on average.
The participants were treated using the cannabis flower with varied combustion methods including vape, pipe, and joint. THC potency on average was 20 percent and limited to 30 percent. CBD potency was on average 5.7 percent and limited to 30 percent. After using cannabis, participants rated symptoms on average to be 2.2, which was a decrease of 4.5.
The results indicated the cannabinoids in cannabis decreased symptoms of insomnia. But the study involved using the cannabis flower, which contains several cannabinoids. It’s difficult to determine if relief from insomnia was due to CBD or another cannabinoid.
In another study published in the Permanente Journal, 72 adults with anxiety and poor sleep were involved. The participants completed anxiety and sleep assessments at the start of the study and at the first-month follow up. Study participants were given 25 mg of CBD in capsule form. Those that predominantly had sleep complaints took the dose in the evening. Participants that had anxiety as their predominant complaint took CBD in the morning.
After the first month, anxiety scores decreased in 79 percent of the people. Sleep scores improved in 66 percent of the participants, which indicated less trouble sleeping. The results suggest that CBD decreased sleep difficulties in many of the participants. But while the decrease in anxiety symptoms remained steady for the duration of the study, the sleep scores fluctuated over time.
Several smaller studies have also supported the use of CBD oil to improve sleep. For example, a case study involving a 10-year-old girl with post-traumatic stress disorder and poor sleep was treated with CBD. A trial of 25 mg of a CBD supplement was administered at bedtime. An additional 6 to 12 mg of CBD was given via a sublingual spray during the day for anxiety. Sleep quantity and quality gradually improved over five months.
Though there is plenty of supporting evidence that shows CBD and cannabinoids can improve sleep, the results are not conclusive and more research needs to be done.
Forms of CBD
CBD is extracted from the cannabis plant and known as CBD oil. But it can be a little complicated. CBD may be extracted from either the marijuana or hemp plant, which are both strains of the Cannabis sativa plant. But they are harvested differently. Hemp comes from the seeds and stalks of the plant, which contains less THC than marijuana.
Because the THC content in CBD oil may vary, depending on the state it’s sold, there may be restrictions. For example, in some states, CBD oil is sold legally if all of the THC is removed. If CBD oil still contains THC or other cannabinoids, it may only be sold in states that have legalized marijuana use.
Depending on the laws in your state, you may need a doctor’s prescription for CBD oil. But laws continue to change quickly, so in the near future, it may be different.
CBD oil can be placed under the tongue. It may also be infused in different products including the following;
- Edibles: Various types of edibles infused with CBD oil are available including gummy bears, cakes, and cookies. Edibles usually list the concentration of CBD in milligrams.
- Vaporing: CBD extract can be used in a vaporizer or vape pen. As the extract heats up, it creates a vapor that is inhaled.
- Tinctures: CBD also comes in tinctures. A few drops of the liquid can be added to drinks.
CBD oil is available in different concentrations. Since research is ongoing, the exact dose to treat sleep issues may not be fully known. It might take some trial and error to determine what works best.
Because there are so many different ways to ingest CBD, there are tons of CBD products to choose from. If you aren’t sure where to start, here are the CBD products we recommend to try if you want to improve your sleep.
Overall, there is scientific research that supports the theory that there are CBD health benefits. While more research needs to be done, the use of CBD can potentially decrease your symptoms of insomnia and help you get more quality sleep. If you struggle with sleep issues, the best first step is to consult your doctor and learn more about causes and treatments.
What’s the Best CBD Dosage for Sleep?
Home » Blog » What’s the Best CBD Dosage for Sleep?
You plump your pillow, maneuver from one side of the bed to the other, and practice breathing deeply—in, 1, 2, 3, 4; out, 1, 2, 3, 4—then turn your head to the clock on your bedside table. It’s 2 a.m. and you still haven’t gotten an ounce of sleep.
When you don’t sleep restfully, everything else suffers—your concentration, energy levels, and athletic performance can all falter if you’re unable to catch those precious Z’s.
Thankfully, CBD is a catch-all when it comes to rest and relaxation. Whether you’ve learned the connection between CBD and cortisol and want to try CBD for stress management or better sleep regulation, finding the right dosage is important. However, there isn’t a one-size-fits-all rule when it comes to CBD dosage for sleep. Instead, it depends on many factors like your body composition and the quality of your CBD product, which this guide will explore.
- Factors like your body composition and lifestyle habits will affect the effectiveness of CBD. However, it’s generally recommended to take 2.5 mg/1 kg of body weight when first starting.
- To determine the best CBD dosage for you, you’ll need a little patience. Experiment with dosage to find your sleep time sweet spot.
- When purchasing CBD products to incorporate into your nightly routine, find a product that’s third-party tested to ensure you’re getting a high-quality product.
How to Determine the Right CBD Dosage for Sleep
When you’re tired, everything can feel off-kilter. That’s where CBD comes in. When ingested, CBD interacts with the body’s endocannabinoid system to help maintain homeostasis throughout the body.
And taking a few CBD gummies or placing a few drops of CBD oil under your tongue before you tuck yourself into bed may help support more restful sleep.
Generally, it’s recommended to take 300-600 mg of CBD a day to support stress management, or 2.5 mg per kilogram of body weight. However, it’ll take some time and patience before you can determine how much CBD you’ll need to sleep soundly.
The right dosage for you depends on two factors:
- Your body composition
- The CBD product you choose
Let’s take a deeper dive into the specifics.
Step 1: Consider Body Composition Factors
When incorporating CBD into your nightly routine, it’s important to understand how it may affect your body based on your composition and lifestyle choices:
- Your weight – The more you weigh, the higher dosage of CBD you might need to fully feel the effects. In contrast, individuals who weigh less may need less CBD since it takes less time to metastasize throughout the body.
- Your metabolism – The speed with which your body breaks down and uses the CBD you consume will also impact how much CBD you need to support sleep. If you have a faster metabolism, you might feel the effects more quickly but they may wear off faster too.
- Your medication(s) – Some medications can interfere with your normal sleep cycle , which, in turn, may impact the effectiveness of CBD for sleep support. If you do take regular medication, you should check with your doctor before adding CBD to your sleep routine to ensure that it’s safe for you.
- Your eating habits – If you take an edible form of CBD, like a gummy or oil, it might take longer to take effect if you have a full stomach, as it will slow digestion.
Step 2: Identify CBD-Related Factors
Next, you should also pay close attention to the CBD product you’ve chosen to incorporate, as several factors may affect the effectiveness of the supplement:
- Quality of the product – The better the quality of the CBD product, the more likely it is to be effective. CBD isn’t regulated by the FDA, which means some products may not follow through on the promises made by their label. As such, limit yourself to products that have been reviewed by a third-party lab to ensure that you’re getting what you pay for.
- CBD potency – There are three different kinds of CBD: full-spectrum CBD, broad-spectrum CBD, and CBD isolate. Of these three, full-spectrum undergoes the least processing. It retains all of the naturally occurring compounds of the plant it’s derived from, including trace amounts of THC. On the other hand, CBD isolate only contains pure CBD, ultimately making it the purest of the three.
- Amount of CBD per serving – This can get a little tricky. Some products will list the amount of CBD in the entire package , while others list the amount per serving. It’s important to make sure you’re reading the label closely so you know how many milligrams of CBD you’re taking.
- Product purpose – Different CBD products provide support for different conditions. Some topical CBD lotions may help ease joint stiffness , while CBD oils might be used to promote restful sleep.
Which CBD Products Can You Try for Sleep Support?
So, what is the best way to take CBD for sleep ? Most CBD products can support a restful night of sleep and are available in the following forms:
- Topical CBD – If you have trouble sleeping because you experience joint discomfort, CBD topicals like lotion or balm may help provide some relief and keep you comfortable throughout the night.
- CBD gummies – If you’re looking for support for your overall health and wellness, then you might want to try adding a few CBD gummies to your nighttime routine. A calm and relaxed mindset is ideal before you settle in for sleep.
- CBD oils – CBD oils are placed under the tongue for fast-acting effects. They may help to refocus your mind and release tension from a stressful day. When your mind relaxes, your body can follow.
- CBD capsules – CBD capsules are formulated for rapid delivery so you can feel the effects more quickly. Because CBD and melatonin can go hand in hand, Resilience’s Rest CBD Softgels also contain melatonin to support quality sleep.
- CBD bath bombs – Sleep and recovery work hand in hand. If you find your muscles are sore after a long day, soaking in a bath infused with a CBD bath bomb might help ease your mind and some of your muscle soreness.
How to Fine Tune Your Nightly Routine
Once you’ve determined how your CBD product of choice may affect your body, depending on your weight, metabolism, medications, and eating habits, you can start to experiment with CBD dosages to find what works best for you.
Step 1: Take Notes
First, determining the right CBD oil dosage for sleep support requires that you do a little homework. Don’t worry, it’s not too tricky. To begin, you’ll want to keep a journal with notes on the following factors:
- Hours of sleep – Write down the hours of sleep you get each night. You should also make note of what time you got into bed and what time you woke up. This will help you set a consistent sleep schedule and understand how CBD is affecting your sleep.
- CBD dosage – You’ll also need to write down the CBD oil dosage you take each night. Remember, you should start with a low dosage (2.5 mg/1 kg of body weight), give your body time to adjust, and then determine if you need to up your intake to a higher dose .
- Sleep outcomes – Finally, write down how you slept each night. Did you drift off right away or stare at the ceiling for an hour? Did you wake up periodically throughout the night or did you sleep deeply from the moment your head hit the pillow?
Having this data in writing will help you make informed judgments and decisions about the best CBD dosage to take moving forward.
Step 2: Spruce Up Your Sleep Space
No amount of CBD will support your sleep if your sleeping space isn’t conducive to healthy rest. The CDC recommends making the following adjustments to your sleep environment:
- Create a dark space that blocks light from seeping into the room
- Keep your bedroom cool
- Reserve your bedroom for sleep only
- Maintain a quiet space while you sleep, using earplugs if necessary
You can also get yourself primed for sleep by curating a calming routine before bed. Quiet, relaxation time before sleep helps your brain recognize that it’s time to settle down. To that end, you can unwind by:
- Taking a warm bath
- Reading a book
- Listening to calming music
- Sipping chamomile tea
- Chewing a CBD gummy
You can also reduce the amount of time you spend scrolling through your phone before bed. The blue light emitted from your device can suppress your body’s production of melatonin, making it more difficult to drift off to sleep.
Step 3: Trial and Error
It’ll likely take time to figure out how much CBD for sleep your body requires. However, you should always start with a low dose and then increase the dose gradually as you learn how your body interacts with CBD.
Trust yourself and the process. Your sleep quality impacts other parts of your life, including your ability to manage anxiety and stress and maintain a functioning metabolism. For all athletes, there is even a direct correlation between sleep and athletic performance , so ensuring you’re taking care of any sleep problem that arises is crucial.
Perfect Your Sleep Routine with Resilience CBD
Poor sleep has a tremendous impact on everything from physical health, mental health, concentration, and more. CBD is a great way to help support you in your endeavors to achieve better sleep and take care of your body, but this involves figuring out the CBD dosage you need. There isn’t a single dosage of CBD that will work for everyone—your body composition, overall health, and the quality of CBD you buy will all play a role as you determine the sweet spot for your needs. It’s also critical that you optimize your sleeping environment and eliminate pre-bedtime distractions.
When you’re ready to incorporate CBD into your restful sleep routine, Resilience CBD is your trusted expert. Our premium CBD products come with a Label Accuracy Guarantee™ so you don’t have to lose sleep over the quality of your CBD.
CBD Oil Dosage For Sleep
There isn’t one dosage that will work for everyone, but there are general guidelines. T he U.S. Food and Drug Administration doesn’t have recommendations on how much to take, but e xperts generally recommend 1–6 mg per every 10 lbs of body weight. For example, if you weigh 100 lbs, you could take 10–60 mg daily. The chart below is a handy reference for how much you might start with. You can also use our CBD dosage calculator to quickly find your results.
|Weight and dosage||100 lbs||150 lbs||200 lbs||250 lbs||300 lbs|
|1 mg||10 mg||15 mg||20 mg||25 mg||30 mg|
|2 mg||20 mg||30 mg||40 mg||50 mg||60 mg|
|3 mg||30 mg||45 mg||60 mg||75 mg||90 mg|
|4 mg||40 mg||60 mg||80 mg||100 mg||120 mg|
|5 mg||50 mg||75 mg||100 mg||125 mg||150 mg|
|6 mg||60 mg||90 mg||120 mg||150 mg||180 mg|
CBD products are available in varying doses and sizes. Some products that appear to be large in size aren’t necessarily a large dose of CBD. Remember to check how many milligrams are in each serving.
How much you should take will depend on lots of factors, including your age, your sex, the reason you’re taking it, your metabolic rate (how quickly you metabolize compounds), and the quality of the product
If you’re taking CBD for a serious case of insomnia, or some other condition such as anxiety or depression, you may need to be in the higher range of recommended use. Speak to your doctor about how much you can start with, especially if you have any medical condition. CBD may interact with other drugs that you’re taking, so talk to your doctor to make sure there aren’t any drug interactions.
How to Calculate Dosage If Not Labeled
Capsules and gummies will tell you exactly how many milligrams of CBD are in each serving. With oils or sprays, it may or may not tell you how much CBD is in each drop or spray. If it doesn’t, then you have to do a little math.
Each drop is .05 mL, so if you have a 10 mL bottle, the bottle will contain 200 drops. You work this out by dividing the size of the bottle by the number of drops. If the bottle contains 500 mg of CBD, it will give you 2.5 mg of CBD per drop (500 mg divided by 200 drops). If you want to take 25 mg of CBD, you will take ten drops.
Increasing Your CBD Dosage
It’s a good idea to start slow. Begin on the lower end of the CBD dosage to make sure that you don’t have a negative reaction. CBD has been found to be generally safe, and occasionally users report appetite changes, fatigue, and diarrhea.
Keeping a record of how much you take and how you feel can also be helpful. If after a few days you aren’t feeling much effect, you can slowly increase your dosage. If you’re taking CBD to improve your sleep, track how long it took you to fall asleep, how many times you woke up during the night, how long you slept, and how you felt when you woke up.
One of the best ways to track your sleep is with a sleep app. I’ve tested out several, and my favorite is Sleep Cycle. Besides tracking a lot of basic information about your sleep, it has a great feature where you can add “sleep notes,” such as “30 mg CBD,” “40 mg CBD,” etc. Every night you can check off the relevant sleep note to mark what you did that day, and it will track how well you’re sleeping with each of the different notes. For example, I can see that when I eat a lot of sugar during the day, my sleep quality decreases by 15%. When I take 120 mg of CBD, my sleep quality increases by 20%. When I take 50 mg of CBD, my sleep quality increases by 10%.
It also takes people different amounts of time to experience the effects. There are many reported benefits of CBD, such as pain relief, stress relief, being able to fall asleep faster and sleep deeper, but one of the most common effects of CBD is a sense of calm. Some may feel it within an hour; for some, it may take a few days or even a few weeks. If you don’t notice anything after a week, increase your dose. If you are pretty sensitive to supplements, you may increase the dose every few days until you start noticing benefits. There are no guarantees that you will feel anything different, but you have to give it time.
Another factor is how often you take CBD. Instead of taking your daily intake in one dose, experiment by dividing it in two and taking it twice per day to see if you feel more benefits. As CBD stays in your system for 4–6 hours, you may find it helpful to take it two or more times per day.
What Are the Best Ways to Take CBD?
There are a lot of ways to take CBD, including capsules, tincture, spray, added to a drink, creams, lotions, candy, and in a vape.
If you want to know exactly how many milligrams (CBD dosage) you’re taking, the best way is the capsule (or a gummy) as the bottle will tell you exactly how much is in each capsule. If you’re using a tincture, it’s more difficult to get the exact dose you’re looking for. Another benefit of capsules is that there’s no taste. With tinctures, you can taste more, and the flavor isn’t always great.
The fastest way to feel the effects is to use a tincture or spray. Place the CBD under your tongue and let the mucous membranes in your mouth absorb it for 60 to 90 seconds. Many people will feel the effects in around 20 minutes. If you take it in a capsule, or if you swallow a CBD liquid, it has to pass through your digestive system and be metabolized by your liver, so it could take an hour or two. Using CBD topically is better for dealing with chronic pain in a specific area.
Speed isn’t necessarily the most important factor in choosing how to take CBD. For some people adding it to their drink or smoothie is the most convenient, and for others, a capsule is best. No matter which way you choose, it’s a good idea to time it for the best effect. If you’re taking it to sleep better, you may want to take a capsule a couple of hours before bed, or a tincture 20 minutes before bedtime.
Make sure that you’re taking a high-quality CBD product. If you’re not, it will reduce the chances of you experiencing the benefits, and in rare cases, could cause you harm. Hemp is a bioremediator, meaning that it can extract toxins out of the soil. It was used by farmers in Chernobyl after the nuclear accident to help clean the soil.
High-quality brands will include a certificate of analysis (COA) that shows all of the third-party testing that has been done on the product to make sure that it’s free of toxins and other contaminants.
Can CBD Help You Sleep Better?
There’s a lot of research being done right now on insomnia and CBD, and the results so far are positive. Research published in the National Institutes of Health (NIH) found that when 160 mg of CBD was administered to subjects, they reported sleeping significantly more than those who took a placebo. Another study in the Journal of Pharmacology found that CBD increased sleep time in rats. Yet CBD administered during the day increased the amount of time to fall asleep, suggesting that CBD can make you more awake during the day.
It’s no surprise that CBD can help you get to sleep faster, stay asleep, and get more restful sleep as there are many conditions that CBD is reported to benefit, including, anxiety, depression, joint pain, COPD, diabetes, heart disease, and substance abuse.
Many researchers believe that there’s a connection between CBD’s benefits for reducing anxiety and increasing sleep.
There’s a lot of research being done on CBD as it’s become popular since the Farm Bill was passed. In 2018 the United States Food and Drug Administration (FDA) approved the first CBD-based treatment to help control epileptic seizures in Lennox-Gastaut syndrome and Dravet syndrome. There may be more CBD-based products approved by the FDA in the future.
On February 19, 2021, the Journal of Cannabis Research surveyed 522 adults that use cannabidiol. Below are the responses when asked “how does cannabidiol affect your sleep?”
How Does CBD Affect Your Sleep?
Moltke, J., Hindocha, C. Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. J Cannabis Res 3, 5 (2021).
Does CBD Make You High?
THC ( tetrahydrocannabinol)is the compound in marijuana that makes people high. Though CBD and THC come from the same plant, CBD doesn’t cause a person to get high. Some CBD products have trace amounts of THC (3% or less), but research from the Netherlands suggests that CBD can counteract some of the effects of THC. Some marijuana growers have even developed strains containing higher levels of CBD that make for a much milder high.
Will You Fail a Drug Test?
As CBD won’t make you high, it won’t cause you to fail a drug test. THC can affect a person’s mood, coordination, time perception, concentration, and memory, and even cause hallucinations. Occasionally THC can cause negative side effects including anxiety, rapid heart rate, and short-term memory recall issues. CBD doesn’t have the compounds that cause these effects.
If someone was taking a large amount of CBD, over 1,000 mg per day, they could trigger a false positive on a drug test. Most people take between 100 mg and 200 mg per day.
There are few known side effects of taking CBD. Those who do experience negative effects will have changes in appetite, fatigue, or diarrhea.
CBD can interact with other pharmaceuticals, so if you plan on using it, speak to your doctor. CBD can interact with any drug metabolized by cytochrome P450 enzymes, which can include:
- immune modulators
- angiotensin II blockers
- oral hypoglycemic agents
- HMG CoA reductase inhibitors
- calcium channel blockers
- HIV antivirals
Is CBD Addictive?
According to the National Institute on Drug Abuse, CBD isn’t addictive, and when someone stops using it, there are no withdrawal symptoms.
How CBD Works
CBD prevents the stress response that starts in the brain by activating the adenosine receptor in our endocannabinoid system, which controls the physiological response to stress called the hypothalamic-pituitary-adrenal axis (HPA). This process starts when the brain perceives something that it believes could cause us harm.
The first part of the chain is the amygdala, which contributes to emotional processing. The amygdala signals the hypothalamus which then signals the adrenals and the rest of the body. The adrenal glands send adrenaline into the body to make the heart beat faster, the muscles and organs receive more blood and oxygen, the brain receives more oxygen, and glucose and fat are released into the bloodstream. The person is now able to run faster or fight harder as they have more energy and are more aware.
When someone has chronic, low-level stress, they’re unable to sleep because this stress response is preparing them to run and/or fight, not sleep. Researchers believe that this may be the main way that CBD helps insomniacs get to sleep, by reducing or shutting off the HPA stress response.
How to Store CBD
Like many other oils, CBD can break down when exposed to heat, oxygen, or light, hence many CBD products are in dark brown or colored containers. The best place to store your CBD products is in a cool and dark place (a refrigerator is a good option). If you don’t expose your CBD products to heat, oxygen, or light, most products will last up to a year.
CBD Dosage Frequently Asked Questions
Here are the answers to the most frequently asked questions we receive about CBD dosage.
The U.S. FDA doesn’t have recommendations on how much to take, but experts generally recommend 1-6 mg per every 10 lbs of body weight. If you weigh 100 lbs, you could then take 10-60 mg daily.
Start with a low dose to make sure that you don’t have any negative reactions. If after a few days you aren’t feeling much effect, you can slowly increase your dosage.
If you want to know exactly how many milligrams of CBD you’re taking, capsules are the best. If you want to experience the effects the fastest, using a spray or tincture is best.
Research published in the National Institutes of Health (NIH) found that when 160 mg of CBD was administered to subjects, they reported sleeping significantly more than those who took a placebo.
THC is the compound in marijuana that makes people high. Though some CBD products have trace amounts of THC (3% or less), CBD counteracts the effects of THC. And CBD oils without THC are also available.
If someone was taking a large amount of CBD, over 1,000 mg per day, they could trigger a false positive on a drug test. Most people take between 100 mg and 200 mg per day.
According to the National Institute on Drug Abuse, CBD isn’t addictive, doesn’t cause a high, and when someone stops using it, there are no withdrawal symptoms.
CBD prevents stress that starts in the brain via the adenosine receptor in our endocannabinoid system, which controls the response to stress called the hypothalamic-pituitary-adrenal axis (HPA).