If you’re not already familiar with the endocannabinoid system, that’s not surprising! Scientists didn’t know this important biological system existed until about thirty years ago. Turns out, the body has a whole apparatus that’s based on compounds that are very similar to the compounds found in the cannabis plant. And it has a powerful influence over our health, and how we think and feel throughout the day. The endocannabinoid system also plays a big role in regulating sleep, and may have a significant effect on how we dream.
I’ve been writing periodically about how cannabis interacts with the body in the realm of sleep, mood, cognition and health, and how cannabis and its active components are increasingly seen, studied, and used for their therapeutic properties, to treat sleep disorders and a range of health problems. One important mechanism through which cannabis does its therapeutic work in the human body is by its direct interaction with this system. So, let’s take a closer look at how it works.
What is the endocannabinoid system
It is a system that enables signaling between different types of cells, in order to regulate a whole range of activity in the body. The endocannabinoid system is made up of several parts:
- Compounds that are similar to the cannabinoids found in cannabis, known as endogenous cannabinoids
- Cell receptors that interact with those endogenous cannabinoids, from many types of cells in different locations throughout the body
- Enzymes that produce and release endogenous cannabinoids, as well as break them down after they’ve done their job
What is that job, exactly? Good question! It’s one that scientists are still working to answer, nearly 30 years after the initial discovery of the existence of this biological system. Here’s what we know: at a fundamental level, the endocannabinoid system is to help maintain homeostasis in the body. Homeostasis—sounds like biology class, right? It comes from the Greek word for “steady,” and it refers to the biological stability and balance that living beings need to survive and maintain health. Scientists have identified this system as perhaps the most important in maintaining balance in human physiological function.
To deliver on its fundamental job of maintaining homeostatic balance, the endocannabinoid system gets involved in many of the body’s physiological processes, including:
- Stress, mood, nervous system activity
- Cognitive processes, including memory and learning
- Sleep and maintenance of sleep-wake cycles
There have been at least six endogenous cannabinoids identified to date. These are the cannabinoids that the body produces. The two best known and most well studied are anandamide (ANA) and 2-arachidonoylglycerol (2-AG).
Receptors that communicate with these endocannabinoids are located in cells throughout the body. Two types of cannabinoid receptors have been identified: CB1 receptors and CB2 receptors. CB1 receptors are found in the brain and the central nervous system, with receptors located in the skin, organs, blood vessels and intestinal tract. CB2 receptors are located mostly in cells belonging to the immune system.
Endogenous cannabinoids bind with CB1 or CB2 receptors, triggering signals that a physiological response is required. Cannabinoids can bind with receptors to do things like launch an immune response to pain, increase (or decrease) the production of hormones that regulate mood, stimulate wakefulness or relaxation and drowsiness. And that’s just the tip of the iceberg. Depending on the type of cell that’s being acted upon through a receptor, and the particular endogenous cannabinoid that’s unlocking that receptor and cell, a whole range of biological activity can take place. For example, activation of CB1 receptors in the brain affect how the body metabolizes and stores energy (aka calories).
Cannabinoids from other sources (those found outside the body, aka exogenous cannabinoids) can also interact with the human endocannabinoid system. More on that in a minute.
When you stop to think about it, it’s pretty amazing that this system went undetected for so long, given how broad and significant it is. Scientists discovered the endocannabinoid system in the early 1990s, while investigating the effects of THC, one of the many—and the best-studied—cannabinoids found in cannabis. I’ve written about cannabinoids and their distinct effects on sleep.
Before this discovery, we didn’t know the human body made its own cannabinoids, nor that it had an internal system that interacted with exogenous cannabinoids—those cannabinoids found elsewhere in nature or produced synthetically. Since that initial discovery, scientists have determined that the endocannabinoid system is ancient, in evolutionary terms. It’s been traced back to a presence in living organisms more than 500 million years ago.
How the endocannabinoid system affects sleep
Sleep-wake cycles are an expression of homeostasis in action—a dynamic, ongoing balance of rest and activity that is essential for survival, vitality and health. The body’s own homeostatic sleep drive works alongside circadian processes to move us between sleep and wakefulness throughout the 24-hour day. The endocannabinoid system influences sleep in several ways.
Regulates and modulates sleep-wake cycles. Research shows the endocannabinoid system plays a direct role in the maintenance of daily sleep-wake cycles, through a complex series of cell signaling. The CB1 receptor has been shown to both induce sleep and stimulate wakefulness.
May affect dreaming. The endocannabinoid system exerts an ongoing influence over cognition, emotions, and consciousness in ways scientists are just beginning to understand. Likely for these reasons, this system appears to influence the content and emotional intensity of dreams.
Affects other biological functions that influence sleep. The impact of the endocannabinoid system on the body is vast. It’s work touches on most of the body’s daily functioning and underlying health. It’s effects on these functions can go on to influence sleep indirectly.
Mood. The endocannabinoid system helps to regulate and stabilize mood and stress levels. Mood and stress, in turn, have an enormous impact on sleep. A lot of us are learning that lesson again these days, as the pandemic ratchets up stress and makes emotions more volatile, in turn making it harder to sleep.
Immunity. The endocannabinoid system has a set of receptors—the CB2 receptors—that are primarily connected to immune cells. Through these receptors, the system can activate, suppress, and direct immune function, including the production of inflammation. I’ve written before about the relationship between inflammation and sleep, and how too much of the former can lead to too little of the latter.
Pain perception. A growing body of research has established the endocannabinoid system as important in regulating pain sensation in the body. Both CB1 (central nervous system-based) and CB2 (immune system-based) receptors appear to be involved in pain perception. And drug therapies are in development to treat pain and inflammation by targeting the endocannabinoid system. Physical pain is a major obstacle to sleep—and when pain is chronic, often sleeplessness is chronic too.
Other health conditions. The endocannabinoid system appears to play a role in both disease pathology and disease protection for a range of conditions, including metabolic disorders, cardiovascular disease, cancer and neurodegenerative disease. These disorders—from diabetes to high blood pressure to Alzheimer’s disease– can have a profound impact on sleep.
How cannabis interacts with the endocannabinoid system
Cannabis, which contains its own cannabinoids, has been shown to affect many of the physiological processes that the endocannabinoid system is involved with. Depending on the strain of cannabis, its components can:
- Induce sleep, promote wakefulness, and ease insomnia (I wrote recently about how cannabis may be an effective therapy for insomnia symptoms)
- Help to relieve pain
- Affect stress, alters mood, and promotes relaxation
- Produce changes (often stimulatory) to appetite
- Produce changes to aspects of cognition, including attention, focus, and creativity
We’re still learning how cannabis and its own naturally produced cannabinoids interact with the human endocannabinoid system. It’s a complex, dynamic biochemical process to unpack. We’re learning that different cannabinoids interact in distinct ways with the system. For example, THC, the cannabinoid associated with the “high” of cannabis—and also the object of a lot of attention for its therapeutic value—binds directly to both CB1 and CB2 receptors. This is likely why THC can have such a vivid effect on the body, from triggering hunger to easing pain to promoting a creative state of consciousness.
CBD, another popular, well-studied cannabinoid found in cannabis, appears to relate very differently to the endocannabinoid system. It does not bind to CB1 or CB2 receptors. It may bind to a type of endocannabinoid receptor that has yet to be discovered—but we won’t know until or unless we discover it! CBD appears to change how the body’s CB1 and CB2 receptors interact with the endogenous cannabinoids it makes on its own.
There’s so much to learn here, but the existence of the endocannabinoid system revealed a fascinating connection between the cannabis plant and a core component of the body’s health and sleep promoting biology. This connection may be why cannabis has been used successfully for centuries in natural medicine, and why the plant continues to be at the forefront of therapeutic research for sleep, mood, pain and other health disorders.
Michael J. Breus, PhD, DABSM
The Sleep Doctor™