Our endocannabinoid system (ECS) is a critical layer of our physiology, like our cardiovascular or nervous systems—and it was only discovered in the 1990s.
We’re just scratching the surface of its vital roles in homeostasis and immunity and, perhaps most notably, its role in neurodegenerative disease.
As scientists probe the ECS, they’re finding its influence in nearly all realms of the body. A keen eye toward lifestyle and certain supplements can help keep this system in tiptop shape.
How The Endocannabinoid System Works
Dr. Christina Campbell, a functional medicine practitioner and board-certified osteopathic physician, told The Epoch Times that she began her investigation into cannabinoids when she began suffering debilitating migraines. She had to schedule her emergency room shifts around the migraine attacks, often employing earplugs and sunglasses for relief.
“I was losing half of my life to that,” Campbell said. “Once I dove into the research and saw just how wide-reaching and important this system was … that was when I said, ‘Okay, well, I really need to know everything about this, because how many people can this really help?’
“The endocannabinoid system is incredibly important because it is a master control system.”
The endocannabinoid system can be seen as a layer that builds on top of our nervous system, the vast bodily system made up of cells called neurons. Neurons branch out from the brain and spinal cord and extend throughout our physiology to transmit signals that govern almost everything we do. Neurons communicate with other cells via electrical signals across gaps called synapses that act like traffic intersections of the nervous system.
Generally, these signals stimulate neurons to release neurotransmitters—such as dopamine or serotonin—which are molecules that bind to the receptors of other neurons, determining what kinds of signals are communicated. Usually, the direction of the signal travels from the sender neuron, designated as “pre-synaptic,” to the recipient neuron, designated as “post-synaptic.” However, endocannabinoids are unique in that they flow backward, sending signals from the post-synaptic neuron back to the pre-synaptic, which alters how signals of other neurotransmitters are received by the former. This unique mode of communication, coupled with their widespread distribution and importance in the body, has led to this collection of neurotransmitters, receptors, and enzymes to be conceptualized as the endocannabinoid system.
THC (tetrahydrocannabinol) was discovered in 1964 and was identified as one of the primary psychoactive components of the cannabis plant. It’s responsible for the “high” that marijuana users report. Cannabidiol (CBD) was also discovered as one of the plant’s primary nonpsychoactive compounds. These have become known as phytocannabinoids to indicate cannabinoids that come from the plant itself.
However, it wasn’t until 1990 that scientists discovered the receptor that THC and CBD were binding to, dubbed CB1. Cannabis’s active ingredients weren’t the only thing binding to CB1. Not long after, researchers isolated “anandamide,” (coined from the Sanskrit word ananda, meaning bliss), the first of our body’s own endocannabinoids to be discovered. From there, they detected receptor CB2 and began the ongoing unraveling of how the ECS works.
CB1 and CB2 are typically regarded as the main receptors of the ECS. CB1 is incredibly prolific in the brain, central nervous system, and peripheral nervous system. CB2 is more present in immune cells but is also found to a lesser degree in the nervous system. However, both receptors have also been found throughout the body, including in the cardiovascular system, skeletal muscle, bones, skin, eyes, and reproductive system.
Safeguarding the Brain
Perhaps most noteworthy is the ECS’s role in brain and neurological health. The CB1 receptor has the ability to modulate neurotransmission, meaning that it can alter the way other neurotransmitters function, as described in a 1999 study in The Journal of Neuroscience.
It’s also involved in the creation of neurons and even impacts how the brain wires itself as it matures, as explained in an overview published in Philosophical Transactions of the Royal Society of London in 2012. As reported in the same journal that year, endocannabinoids themselves can even affect both short-term and long-term “plasticity” of neural synapses, a key factor in how the brain forms—or doesn’t form—connections.
Because of its widespread distribution in the brain and nervous system, the ECS has an impact on eating, anxiety, learning, memory, reproduction, metabolism, growth, and development. Subsequently, its malfunction is correlated with the onset of neurodegenerative illness.
A 2007 study in Pharmacological Research found an imbalance in the ECS in patients with Alzheimer’s disease, suggesting its “possible role in inflammatory processes and in neuroprotection.” They also observed that in Huntington’s disease, there was a loss of CB1 receptors and a decrease in endocannabinoids in parts of the brain involved in movement control.
There’s also evidence that the ECS activates when the body suffers neurological injury. In a study published in 2010 in Life Sciences, scientists found that the system activates distinct pathways in response to “pathogenic events or stimuli” to enhance tissue repair and cell survival. They concluded that neuronal injury activates the ECS in the central nervous system as an “intrinsic neuroprotective response.” A study published in Brain in 2007 shows that anandamide was elevated in relapsing multiple sclerosis patients.
Following these findings, researchers have experimented with the therapeutic application of cannabinoids to help protect the brain from trauma. Scientists found that application of CBD “significantly reduced” how much brain tissue died after a stroke in mice, in a 2005 study published in Stroke. They speculated that the effect may come from CBD’s effect of increasing blood flow to the brain.
Even the psychoactive THC has shown the potential to benefit the brain. One study published in Nature Medicine in 2017 found that a long-term low dose of THC helped reverse age-related decline in cognitive ability in mice. Another study, published a year later in Neurotoxicity Research, shows that THC enhanced neurogenesis and improvement in both the learning and memory of rats. However, so far, THC’s medical applications appear limited compared to cannabinoids such as CBD. The compound also comes with risks because of its psychoactive nature.
Campbell explained that cannabinoids can also have a powerful impact on our immunity by reducing inflammation, including by regulating cytokine release. Cytokines are an important immune response to fight off bacteria, viruses, and other pathogens, but the body can also overproduce them, leading to a cytokine “storm,” which is also the mechanism behind certain complications related to COVID-19.
The CB2 receptor is actually present in various types of immune cells and impacts how our immune system responds to infection, atherosclerosis, and even cancer, as noted in a study in Immunogenetics in 2006. A review paper published in Cannabis and Cannabinoid Research in 2016 noted that endocannabinoids such as anandamide could be considered “master regulators” of immunity, given how they can fine-tune how various immune cells function and their ability to modulate inflammation.
In a review paper published in Future Medicinal Chemistry in 2010, researchers wrote that several studies show that cannabinoids downregulate cytokines. In general, they concluded that cannabinoids, both those native to the body and exogenous ones, “constitute a potent treatment modality against inflammatory disorders.”
“Some people don’t have that turn-off switch [for inflammation] that works really well. So this can be a really great way to help reduce inflammation … especially for those people who can’t do it for themselves at all,” Campbell said.
By acting on receptor CB2, anandamide helps maintain the balance of the “immune homeostasis” in our intestines and pancreas, according to a 2017 study published in Biological Sciences. The gut is home to a vast microbiome that requires a delicate balance, a function that the study authors described as “one of the most fundamental properties of the immune system.
Maintaining our Delicate Balance
The ECS also plays a powerful role in our quality of life by helping our bodies autonomously adjust toward homeostasis, our self-regulating process that ensures that we’re surviving and thriving.
For example, in the realm of eating, the system senses whether our body is energy deficient, what gastrointestinal load looks like, and how we experience satisfaction and perceive nutrition from our food, as published in the International Journal of Obesity in 2009.
Endocannabinoids are integral to our reward system. Much research has focused on dopamine and its role in motivating and reinforcing our desire to seek out basic necessities, such as food and sex. However, more research has shown that the pleasurable sensation from rewarding stimuli might be more connected to the activation of the ECS, according to a 2017 review in Neuropsychopharmacology.
In fact, because scientists knew about the ECS’s role in stimulating hunger, they attempted to formulate a weight-loss drug that blocked the CB1 receptor. The drug, known as rimonabant, seemed to work well, but it was soon pulled off the shelf because it was disrupting the ECS from regulating mood, thereby causing some users to become suicidal, as reported in Pharmacology Biochemistry and Behavior in 2010.
Solutions and Supplements
Campbell recommends addressing certain key lifestyle factors to improve ECS function. Among them are stress, systemic inflammation, lack of sunlight, and a disrupted circadian rhythm, which she called “one of the biggest mistakes most of us make in the modern world.”
“The problem is that most of us are chronically inflamed, chronically sick, on multiple medications, over toxic-loaded. Our system is really overstressed, and so we’re not making enough cannabinoids to keep ourselves moving,” she said.
Endocannabinoids are derived from omega-6 and omega-3 fatty acids, as explained in “Cannabinoids in Health and Disease,” published in 2016, but they must be in proper balance for the ECS to function properly. Research has borne out that the ideal omega-6 to omega-3 ratio is about 4 to 1, as reported in Biomedicine and Pharmacotherapy in 2002. Unfortunately, the typical Western diet sits at about 15 to 1, predisposing many people to all kinds of illnesses.
Research in mice has shown that those imbalanced ratios—leading to omega-3 deficiency—can impair the ECS’s functioning in the brain and may have a role in other kinds of disease, as published in a 2017 review paper in Lipids. Stepping up omega-3 consumption can help level off this ratio. Omega-3-rich foods include fatty fish such as salmon, anchovies, mackerel, and tuna; kale; walnuts; and eggs from flaxseed-fed chickens.
Supplementation with phytocannabinoids can be crucial in supporting our ECSs. Campbell recommends a full-spectrum, hemp-derived CBD oil such as Kokua Vida; hemp is a variety of the cannabis plant that’s typically cultivated for industrial use. As such, it has a very low concentration of THC, as opposed to the popularly known marijuana. Campbell serves on Kokua Vida’s scientific advisory board and is one of their affiliates.
When choosing a full-spectrum supplement, she advises consumers to make sure to look out for a certificate of analysis conducted by a third party to ensure high quality and purity. Full-spectrum products generally contain a trace amount of THC, and its psychoactive properties are significantly dampened because all the other cannabinoids “compete” for the same receptors. As of 2018, CBD products derived from hemp are federally legal.
There are also similar supplements without THC that are classified as “broad spectrum.” Narrower in scope, there are also “isolate” products available that only contain one or several types of cannabinoids, such as formulations that only contain CBD.
Campbell also recommended the supplement PEA (palmitoylethanolamide), an endocannabinoid-like fatty acid that can boost our ECSs and complement the use of phytocannabinoids such as CBD. It helps activate CB1 and CB2 receptors by putting the brakes on the body’s breakdown of the endocannabinoid anandamide.
She tells her patients to try different products to see what works best but advocates for full-spectrum supplements as the ideal option.
“Honestly, all across essential oils of all plants, including cannabis … the plant really knows what it’s doing, and all of those different components together, they really work synergistically together,” Campbell said.