A deep dive into the importance of the Endocannabinoid system and how plant cannabinoids, such as CBD and THC, play an integral part in optimizing our health. Guided by Jason Wilson, MS – a science educator and expert on cannabis and cannabinoid science – we break down the What, the Why, and the Endocannabinoid System.
The WHAT
What is CBD?
CBD, or Cannabidiol, is an oily compound found in the sticky resins of the Cannabis and Hemp plant. CBD is only one of many different chemicals of its type produced by Cannabis and Hemp. These compounds are called phytocannabinoid (“phyto” = plant + cannabinoid) produced indirectly in the resins of the plant. Although it has been used for thousands of years by different cultures and civilizations, CBD was not formally discovered and studied until the early 1900s, when researchers isolated CBD from an extract of Minnesota hemp.
Since its discovery, CBD has been investigated to determine whether it holds promise as a medicine for a number of different conditions ranging from epilepsy to arthritis, stress & anxiety, sleep disorders, pain, bacterial and viral infections, cancer, and more. As research has continued to elucidate CBD’s therapeutic potential, and as the hemp industry has begun to legally thrive in the United States, CBD has become a very popular compound for health and wellness.
The Difference between the Hemp Plant vs. the Cannabis Plant
The hemp plant and the cannabis plant are both part of the cannabaceae family. The primary difference between the hemp plant and the cannabis plant is their chemical profiles. Hemp plants are low in THC, a phytocannabinoid that produces intoxicating effects. In the United States, hemp is classified as Cannabis plants that contain less than 0.3% THC. In other countries the limit can be even lower, commonly 0.2%. Thanks to intentional breeding efforts, CBD can now be found in concentrations as high as 20% or 25% in hemp plants intended for CBD-rich resin production.
The Cannabis Sativa plant distinctions – bred and grown in two different ways, with different chemical profiles:
- As Hemp – less than 0.3% THC by dry weight; a federally legal agricultural crop in the U.S.
- As Cannabis – up to 30% THC content; available in restricted adult recreational use or/and medical use states in the U.S.
How is CBD Different from THC?
CBD is markedly different than THC. To start, CBD does not cause intoxicating or euphoric effects like THC does¹. Although CBD is not intoxicating, it is psychoactive, meaning that it affects the brain. It is because CBD is psychoactive that it can have effects on things like mood or memory. The manner in which CBD affects the body is also very different compared to THC.
To discuss the differences in how CBD and THC affect the body, it is important to talk about something called the endocannabinoid system, or ECS. The endocannabinoid system is a physiological system in your body that primarily controls the function of oily compounds that tell your body what to do. That’s why the ECS is called a lipid (oily) signaling system, and it affects just about every part of the body, modulating sleep, mood, pain, fear, appetite, inflammation, and more.
The Endocannabinoid System
The ECS
Unfortunately, the ECS has been largely ignored from medical education. Very few medical schools teach about the endocannabinoid system, which was formally recognized in the late 1990s. The omission of the endocannabinoid system from health, nutrition, and medical practice curricula is partially the result of stigma around the Cannabis plant which makes healthcare professionals wary of discussing cannabinoids, and it is partially the result of how new the research around the endocannabinoid system is – though this research is only new because Cannabis prohibition around the world slowed progress in cannabinoid science considerably.
The ECS consists of three primary components:
- 1. Endogenous cannabinoids – cannabinoids that are produced by your body; whereas phytocannabinoid like CBD and THC (“phyto” = plant + cannabinoid) are cannabinoids that are produced indirectly in the resins of the plant.
- 2. Chemical receptors such as cannabinoid receptors (which are CB1, CB2, and potentially more receptor sites) that those endogenous cannabinoids interact with
- 3. Enzymes responsible for building and breaking down endogenous cannabinoids and cannabinoid receptors
In reality, the endocannabinoid system is much more complex than this simple model. Endocannabinoid system components can function differently in different tissues throughout the body and the break down products of endocannabinoids can be active in the body. Endocannabinoids also interact with a lot of other chemical receptors in the body besides cannabinoid receptors. Researchers have come up with the term “endocannabinoidome” to describe this complex network of systems involved in the functioning of your body’s own cannabinoids.
What Does the ECS Do in Humans
It is often said that the endocannabinoid system is a homeostatic regulator, meaning that it tries to help keep all of the body’s systems in balance so that it can function optimally. Cannabinoid researcher Raphael Mechoulam and colleagues have speculated that perhaps the ECS does for fatty compounds in the body what the immune system does for proteins in the body² – namely preventing things from getting out of control by limiting the activity of certain compounds when they are too active, and encouraging the activity of certain compounds when they are not active enough.
In 1998, cannabinoid researcher Vincenzo di Marzo published a paper that characterized the endocannabinoid system and its functions for the first time, stating that the primary functions of the ECS seem to be to help the body “relax, eat, sleep, forget, and protect.”³ Despite our expanding understanding of the functions of the ECS, this basic characterization still rings true.
Relax
Cannabinoid receptors (CB1 & CB2 receptors) are critical parts of our central nervous systems. In fact, the CB1 receptor is the most abundant chemical receptor of its type present in the brain⁴. Additionally, other chemical receptors that are associated with mood, like serotonin receptors and dopamine receptors, are involved in the activities of the endocannabinoid system. Moreover, the endocannabinoid system regulates glutamate, an excitatory compound, and GABA, an inhibitory compound, which are both involved in anxiety and relaxation⁵. It is no wonder then that cannabinoids can have profound effects on things like mood, stress, and relaxation.
Eat
The endocannabinoid system is intimately linked to our feelings of hunger and satiation. In fact, this connection is so strong that researchers identified that in rodents, a newborn will not suckle or feed without early stimulation of cannabinoid receptors in the body⁶. The reason that THC-rich Cannabis elicits feelings of hunger often called “the munchies” is because THC directly stimulates CB1 receptors in the body which go on to tell the brain that the body needs food. Overactive CB1 receptors can prevent a person from feeling satiated, instead being subjected to a constant state of hunger.
In addition to modulating feelings of hunger and satiation, the endocannabinoid system is also directly linked to gut activity. Cannabinoids influence the diversity and distribution of microorganisms that live in the stomach and intestines that assist in the processing of foods and medicines. Cannabinoids can also influence the way that the liver metabolizes compounds.
Sleep
The endocannabinoid system is associated with sleep regulation including the regulation of sleep cycles, like REM. When CB1 receptors are blocked, or antagonized, people tend to feel more awake. Whereas when CB1 receptors are stimulated, people tend to feel tired or sleepy. It has been shown that CB1 receptor stimulation can promote the release of a compound called acetylcholine in the body, which is directly associated with sleep⁷. However the exact mechanisms behind how the endocannabinoid system affects sleep still remain to be understood.
Forget
It is now known that another function of the ECS is to help control what we remember and what we forget. CB1 receptors are densely located on an area of the brain called the hippocampus, which among other things is primarily responsible for controlling memory⁸. While it is often considered better to remember than forget, forgetting is actually a critical part of our psychology. If you remembered every detail about your day all the time, you would have trouble functioning in the world. For individuals with post-traumatic stress disorder, sometimes the brain has trouble forgetting a painful memory or even replays that memory over and over again, causing the person distress. In this scenario, forgetting is therapeutic, and researchers are exploring ways that cannabinoids and other endocannabinoid system modulators may help treat conditions like PTSD that can benefit from enhanced forgetting⁹.
Protect
CB2 receptors are found all throughout the body, but dominantly throughout the immune system, which has led researchers to speculate that CB2 receptors may be critical components of a protective system of the body that helps ensure that the immune system functions properly¹⁰. Additionally, exogenous and endogenous cannabinoids can act as antioxidant compounds that are able to protect cells from oxidative damage by scavenging free radicals¹¹. This protective effect has led to cannabinoids quickly becoming a focus for researchers to find better ways to prevent and treat traumatic brain injuries and other physical traumas¹².
Beyond this basic characterization of “relax, eat, sleep, forget, and protect,” we also know that theendocannabinoid system is involved in other processes like reproduction and development. As researchers learn more about the endocannabinoid system, the way we characterize the endocannabinoid system will likewise expand and become more complex.
The WHY
CBD and The Endocannabinoid System
So back to how CBD affects the body differently than THC! CBD interacts with these cannabinoid receptors, and affects the endocannabinoid system, very differently than THC. While THC elicits its effects primarily by stimulating cannabinoid receptors in the body, CBD does not interact with cannabinoid receptors very much directly, and instead elicits effects through a variety of other mechanisms in the body, ultimately indirectly stimulating the body’s endocannabinoid system by making the body produce endocannabinoids and helping those endocannabinoids circulate in the body longer.
How CBD Helps with Anxiety
Some of the primary ways that CBD might be able to affect anxiety, that we know of so far, are through several mechanisms:
1. Inhibiting FAAH and increasing Anandamide (improving the endocannabinoid system)
2. Modulating excitatory signaling (affecting the “volume” of brain signaling)
3. Manipulating Serotonin receptors (affecting mood directly)
For a fuller discussion, please visit – Stress & Anxiety – How CBD Can Help.
How CBD Helps with Sleep
Based on current data, it seems that CBD might be able to affect sleep through several primary effects: pain reduction, dream suppression, stress reduction, and somnolescence. Depending on why someone is having trouble sleeping, any one of these effects might contribute to a better night’s rest.
For a fuller discussion, please visit – CBD & Sleep – How Does CBD Affect Sleep?
How CBD Helps with Pain
CBD-rich hemp extracts may be able to influence pain in several ways – by modulating the way the brain signals to tell you that you are experiencing pain, by reducing inflammation which can cause or exacerbate pain sensations, and by distracting the mind away from focusing on the sensation of pain.
For a fuller discussion, please visit – CBD & Pain – Managing Pain with CBD.
More Ways to Help the ECS
Exposing the ECS to plant cannabinoids like THC or CBD is only one of many ways to help take care of the ECS. You can also support your ECS through a diet rich in whole foods and fatty acids, regular movement and exercise, and meditation. Diet ultimately helps provide your body with the tools needed to build endocannabinoids and other important chemicals in the body. Movement and meditation also can stimulate the production of endocannabinoids in the body.
¹ Russo E. 2011. Taming THC: potential cannabis synergy and phytocannabinoids-terpenoid entourage effects. Br J Pharmacol. 163(7): 1344-136
² Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res. 2012. 50(2): 193-211
³ Di Marzo, V. ‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible physiopathological relevance. Biochim Biophys Acta. 1998. 1392 (2-3):153- 75
⁴ Kendall DA, Yudowski GA. Cannabinoid receptors in the central nervous system: their signaling and roles in disease. Front Cell Neurosci. 2016. 10: 294
⁵ Pretzsch CM et al. Effects of cannabidiol on brain excitation and inhibition systems; a randomized placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacology. 2019. 44: 1398-1405
⁶ Fride E, Ginzburg Y, Breuer A, Bisogno T, Di Marzo V, Mechoulam R. Critical role of the endogenous cannabinoid system in mouse pup suckling and growth. European Journal of Pharmacology. 2001. 419(2-3): 207-214
⁷ Murillo-Rodriguez E, Poot-Ake A, Arias-Carrion O, Pacheco-Pantoja E, de la Fuente-Ortegon A, Arankowsky-Sandoval G. The emerging role of the endocannabinoid system in the sleep-wake cycle modulation. Central Nervous System Agents in Medicinal Chemistry. 11(3): 189-196
⁸ Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M. The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. Journal of Neuroscience. 2006. 26(11): 2991-3001
⁹ Berardi A, Schelling G, Campolongo P. The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): from preclinical findings to innovative therapeutic approaches in clinical settings. 2016. Pharmacological Research. 111: 668-678
¹⁰ Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res. 2012. 50(2): 193-211
¹¹ Gallelli CA. Calcagnini S. Romano A. Koczwara JB. De Ceglia M. Dante D. Villani R. Giudetti AM. Cassano T. Gaetani S. Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues. Antioxidants. 2018, 7, 93
¹² McCarron RM, Shohami E, Panikashvili D, Chen Y, Golech S, Strasser A, Mechoulam R, Spatz M. Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG). In: Kuroiwa T. et al. Brain Edema XII. Acta Neurochirurgica Supplements. Vol 86. 271-275
Written in collaboration with Jason Wilson, MS – a science educator, natural products researcher, an expert on cannabis and cannabinoid science, and creator of the Curious About Cannabis Podcast.
