The endocannabinoid system: what is it?


The endocannabinoid system: what is it?

Your body is a lot like a symphony—or the chorus of a Mumford & Sons song. It likes to be in harmony. This inner harmony is called “homeostasis,” and the master conductor that keeps everything balanced is your endocannabinoid system.

The endo-what?

The endocannabinoid system (ECS) is a bona fide body system right up there with the digestive, cardiovascular and reproductive systems.

“The ECS is an immensely important physiological system that orchestrates much of the communication within and between organs to help maintain health, well-being and balance,” says Carl Germano, RD, CNS, author of Road to Ananda: Simple Guide to the Endocannabinoid System, Hemp Phytocannabinoids/CBD and Your Health.

While “regulator of internal balance” sounds nice, the ECS has practical downstream effects on things that are much more concrete.

“The ECS governs neurotransmission involved in the regulation of mood, memory, reward, appetite, anxiety, stress and more,” says Germano.

And that’s just the beginning—Germano says the ECS also plays a key role in everything from pain signaling to bone building.

Yet the ECS was discovered only in 1992. It took so long to find because this new system’s framework is tiny. It’s seen only microscopically on cell membranes—the skin of cells. Here there are receptors, which act as keyholes. Potential keys can be anything from nutrients to viruses. When keys fit into keyholes, the door to the cell is opened and things happen.

“Receptors are waiting for a message from outside the cell,” says Alex Capano, DNP, a faculty member and senior fellow at the Lambert Center for the Study of Medicinal Cannabis and Hemp at Thomas Jefferson University in Philadelphia. “Then they translate and communicate that message to inside the cell, [which] then influences activity.”

Unlocking the system

The ECS is a sprawling network of specific receptors on cells throughout the body: CB1 receptors, located primarily on the surface of cells in the brain, and CB2 receptors, which are frequently found on cell walls at the periphery of the nervous system.

“These are receptors that regulate everything from sleep-wake cycle, hormonal balance and inflammation to immune response,” says Capano.

So what are these receptors waiting for? How do we unlock the endocannabinoid system?

You’ve probably noticed the word “cannabinoid” embedded in the system’s name. Cannabinoids are chemicals in the Cannabis sativa plant (they’re also called “phytocannabinoids”). And yes, cannabinoids in both marijuana and hemp—two iterations of the same cannabis plant—affect the ECS.

When marijuana’s active agent, a cannabinoid called THC (tetrahydrocannabinol), interacts with the CB1 receptor, the brain becomes buzzed. But what’s truly fascinating is how hemp’s main cannabinoid—that hot new supplement ingredient called CBD (cannabidiol)—acts on the ECS.

First of all, “CBD does not produce the intoxicating effects that THC produces,” says Germano. Secondly, CBD is not actually a key to the CB1 receptor, but it can still affect cell activity. Think of a doorbell ringing—you might get up from your chair, maybe quickly pick up a thing or two and glance out the window … but you might not engage directly with the visitor.

“CBD doesn’t really bind to receptors,” says Capano. “It just alters the activity in the cell in multiple ways and pathways, many of which we have yet to fully understand.”

Further exploration of CBD will likely be unleashed with the recent passage of the 2018 Farm Bill, which makes way for the government to fund research into all areas of hemp, including CBD. The science still needs to catch up to the anecdotes that abound around how CBD affects the human body,* but we’re slowly beginning to comprehend how CBD interacts with the ECS—including how they work together to bring more bliss into our lives.

Powering the system

Another major component of the ECS are two pre-existing compounds generated within the body, anandamide and 2-AG. These are known as “endocannabinoids,” and—you guessed it—they’re keys to the endocannabinoid receptors. Anandamide takes its name from ananda, the Sanskrit word for “divine joy” or “bliss.”

“Anandamide attaches to the CB1 receptor the way THC does,” says Germano. “While THC is very potent in triggering intoxicating effects, anandamide is much weaker in this respect. We know anandamide is associated with the ‘runner’s high’ involved in reward and mood.”

Runner’s high? Divine joy? Bliss? Who doesn’t want more of that? That’s where CBD comes in. Anandamide is influenced by CBD, which prolongs the existence of this bliss molecule.

“CBD works through multiple mechanisms of action, one of which is by blocking the enzyme that metabolizes anandamide,” says Capano.

One fascinating paper from 2018 revealed that if that specific enzyme is blocked (so it can’t degrade anandamide) in people with post-traumatic stress disorder (PTSD), they may have less severe stress responses. This research ought to lead to other studies using cannabinoids like CBD to block the bliss-busting enzyme.

The Cannabis sativa plant actually contains more than 100 different cannabinoids, and it’s anybody’s guess at this point what effect these may have on the ECS. We may soon be hearing about CBG or CBN or THCV. Hemp also contains other important compounds, like terpenes and flavonoids (see “The entourage effect”).

Supplements at your local natural health retailer, meanwhile, are starting to reflect this complex picture. You may not see simply “CBD” on all labels. Instead, terms like “hemp oil” or “full-spectrum hemp oil containing CBD” or “cannabinoid complex” are gaining ground.

Supporting the system

Endocannabinoids like anandamide and cannabinoids like CBD aren’t the only things that support the ECS. Lifestyle choices, including simple physical activity, can both reinforce the ECS and otherwise optimize health and wellness. The implications are big: Research is demonstrating that a lack of endocannabinoid activity may be associated with a variety of intractable syndromes, from fibromyalgia to migraines to IBS.

“The endocannabinoid system is impacted by a myriad of lifestyle behaviors, such as eating habits, movement activities and yoga practices,” says Laura Lagano, RDN, co-founder of the Holistic Cannabis Academy and author of The CBD Oil Miracle. “You can also help support your endocannabinoid system with stress-reduction techniques, including meditation and aromatherapy.”

Germano says taking cannabinoids from hemp along with omega-3 fatty acids is like taking a “‘multivitamin’ for the ECS.” Preliminary research shows omega-3 deficiency can make cannabinoid receptors not as active. Plus, omega-3 fatty acids help the body produce endocannabinoids. “I cannot overemphasize the importance of looking above and beyond just CBD,” says Germano.

Also not to be overlooked are complementary supplement ingredients that support specific health concerns—valerian or melatonin for sleep, ashwagandha or L-theanine for stress and curcumin for inflammation. You will find these types of ingredients in some hemp oil supplement formulations.

Balancing the body

You know now what works on the ECS. But how does the ECS work on the whole body? Basically, when the body is stressed, the ECS appears to increase both the amount of endocannabinoid signaling as well as the number of endocannabinoids themselves. That’s the body trying to naturally counter stress with bliss. Between the two is normalcy. Homeostasis. Internal harmony. (Mumford & Sons-caliber harmony, even!)

There’s still much more to learn, though. While researchers are beginning to see cannabinoids’ effects on an already impressive range of health states—from anxiety to inflammation to pain—CBD and other parts of the hemp plant may have a much bigger role to play in our health in the future thanks to the ECS. It’s the conductor of our internal symphony, directing all body systems in concert, and we’ve only heard the first few notes.

The entourage effect

The hemp plant contains many components that can affect human health and internal balance. CBD may be the most famous one, but it’s not the only one.

The hemp oil supplements you buy usually top out at perhaps 15 percent CBD, with the rest of the oil containing other cannabinoids, terpenes, flavonoids and plant parts. Many people believe there’s more power in the sum of the plant—that the pharmaceutical model of isolating single chemical constituents can’t measure up to the teamwork of total plant synergy. This concept is called “the entourage effect.”

“The entourage effect means that the whole plant is better than isolated compounds,” says Alex Capano, DNP.

Carl Germano, RD, CNS, says, “There is not one ginsenoside in ginseng. There is not one ginkgolide in ginkgo. There is not one curcuminoid in [turmeric]. So why does anyone expect that one phytocannabinoid (CBD) is responsible for the total activity that hemp provides?”

Researchers have begun to validate this whole-plant approach. A study on mice found that a full-spectrum hemp material was superior—and at a lower dose—to just isolated CBD for reducing inflammation and pain in study subjects. Other research has shown terpenes and flavonoids in the cannabis plant may increase blood flow to the brain and kill respiratory pathogens.

“If you look at the science, it’s incredibly supportive,” says Capano of the entourage effect.

All the terms you’ve ever wondered about

Endocannabinoid system (ECS): A network of receptors found on cell membranes throughout the body that affects the central nervous system and is seen as being responsible for keeping the body in a state of balance, or homeostasis. The ECS appears to help regulate a range of body actions and conditions, from anxiety and pain to depression and memory.

Cannabinoids (also called phytocannabinoids): Plant chemicals that are the active constituents of the Cannabis sativa plant, like THC and CBD, that interact with the ECS and produce physiological effects.

Endocannabinoids: These are compounds produced in the body, principally anandamide and 2-AG, that attach to ECS receptors and then elicit numerous effects on mood, pain signaling, sleep cycling and more.

CBD: Cannabidiol, one of more than 100 different cannabinoids found in the Cannabis sativa plant. While CBD has a range of health effects, getting high is not one of them. CBD as an isolated compound is listed as a Schedule V controlled substance, akin to cough syrup. CBD as part of hemp oil (see below) is not considered a controlled substance.

Hemp oil: A full-spectrum extract of the flowering parts of the hemp plant that includes CBD. Hemp seed oil, on the other hand, is oil pressed from the hemp seeds and is rich in omega-3 fatty acids, not CBD.

Hemp:Cannabis sativa, the same genus and species as marijuana, only with THC levels lower than 0.3 percent. Hemp is the source plant for hemp oil containing CBD. Hemp has thousands of other uses, from nutrition to textiles, fiber to fuel and paper to bioplastics.

Marijuana:Cannabis sativa that’s grown with high enough levels of THC to exert a psychoactive effect—technically anything more than hemp’s 0.3 percent but in practice, usually more than 10 percent. This is the plant for sale in dispensaries—shops that offer medical and recreational products, traditionally found as flowers (aka buds, used to roll joints).

THC: Tetrahydrocannabinol, the primary cannabinoid that gives marijuana its psychoactive effect.

Cannabis: A larger group of plants including Cannabis sativa, Cannabis indica and Cannabis ruderalis. While cannabis is technically also hemp, cannabis is more commonly used as a synonym for marijuana.

Terpenes and flavonoids: Terpenes are molecules reponsible for the aromatic properties of the cannabis plant. Terpenes are found in other plants as well, like cinnamon and ginger. The hemp plant contains an estimated 20 flavonoids (aka plant pigments) that are responsible for a range of health effects, from anti-inflammatory to antioxidant.

Entourage effect: The idea that the hemp plant’s best health effects come from all of its components working together. This includes hemp’s cannabinoids, like CBD, as well as other parts, like terpenes and flavonoids.

*To learn about the research that does exist on CBD’s health effects, head to and read the first article in this series, “CBD: What does the science say?” (Spoiler: CBD is being researched for its effects on everything from pain to insomnia to stress.)


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