cbd oil for pain endocannabinoid system ecs

Our Endocannabinoid System and Chronic Pain

An overview of our endocannabinoid system, its correlation to chronic pain and available treatment options.

By Rowena Chua, MD

June 17, 2019


Cannabis is a plant-based product that has been used medicinally for at least 4,000 years 1 . Widespread medicinal use never materialized because the plant produces both therapeutic and psychoactive effects. Federal restriction of cannabis first occurred in 1937, with the passage of the Marihuana Tax Act. In 1996, California became the first state to permit legal access to and use of botanical cannabis for medicinal purposes under physician supervision. Today, the support towards legalization continues to reach new highs 2 . The purpose of this article is to provide you with an overview of our endocannabinoid system, its correlation to chronic pain and review treatments that are available.

Discovery of a New System in the Body

In the 1960s, scientists studying cannabis (marijuana) identified and isolated 2 compounds: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). They called these compounds “cannabinoids” since they were derived from the cannabis plant. In the 1990s, scientists discovered the receptors where THC and CBD would attach to. These receptors were found initially in rats, then soon after in humans. From there they discovered that a whole molecular system exists within our body. It was named the “Endocannabinoid System” because of the role that cannabis played in its discovery 3 .

The endocannabinoid system is now considered one of the systems in our body, along with the nervous, digestive and cardiovascular system among others.

What is the ECS?

As a master regulatory system within our body, the endocannabinoid system (ECS) has a strong effect on other systems in our body. It is one of our body’s tools for maintaining homeostasis and balance 4 . Important components of the ECS are cannabinoid receptors and endogenous cannabinoids.

Cannabinoid Receptors: CB1 and CB2

Located throughout the body, cannabinoid receptors are part of our ECS. There are 2 main cannabinoid receptors: CB1 and CB2. CB1 receptors are found predominantly in the brain, while CB2 receptors are mostly found in the immune system 5 . The endocannabinoid system is now considered one of the systems in our body, along with other major systems that include the nervous, digestive and cardiovascular systems among others.

Endogenous Cannabinoids: Anandamide

In 1992, scientists discovered what binds with cannabinoid receptors— Anandamide, one of the cannabinoids that our body produces 6 . It was named after the Sanskrit word “ananda” meaning “bliss”. It’s found to be directly correlated with improved mood, reduction of depression and anxiety 7 .

The ECS regulates a host of physiological processes including mood, memory, appetite, muscle control, immune function, inflammation, as well as pain levels 8 .

ECS Deficiency

Like other systems in the body, the ECS can be thrown out of balance due to trauma, stress or toxins. Clinical endocannabinoid deficiency can be associated with various conditions such as migraines, fibromyalgia, irritable bowel syndrome, inflammatory and neurologic conditions 9 . If our body doesn’t produce enough endocannabinoids, then supplementation may be needed.

Exogenous Cannabinoids: CBD & THC

Exogenous cannabinoids, found outside our body, come from plants. If our body does not produce enough anandamide, we can supplement with plant cannabinoids. The 2 main exogenous or plant cannabinoids are CBD and THC.

THC (delta-9-tetrahydrocannabinol)

THC is the main component in marijuana, eliciting the “high”, or psychoactive effect. For this reason, it is highly regulated. THC binds primarily to CB1 receptors, which are abundant in the brain. THC has also been found to have beneficial effects including: pain relief, decreased inflammation, relaxed muscles and increased appetite. However, too much THC can induce anxiety and psychosis 10 .

CBD (cannabidiol)

CBD, on the other hand, does not produce a psychoactive effect or “high” and actually counters the effect of THC. CBD helps increase our supply of anandamide. CBD has also been found to have beneficial effects including: pain relief, enhanced sleep, decreases in inflammation, anxiety and appetite. There are minimal risks or side effects with CBD 10 . In 2018, the World Health Organization declared CBD safe and well tolerated in humans. It is now considered a benign compound and there are several medical applications for CBD 11 .

CBD (Cannabidiol) THC (Delta-9-tetrahydrocannabinol)
No psychoactive effect Elicits the "high"
Counteracts effects of THC Highly regulated
Helps increase anandamide Binds primarily to CB1 receptors
Pain relief, anti-inflammatory, anti-anxiety, anticonvulsant, decreases appetite, enhances sleep Pain relief, anti-inflammatory, muscle relaxant, anti-spasmodic, increases appetite
Minimal risks Can induce anxiety and psychosis

Cannabis Sativa Plant Family: Marijuana & Hemp

So where do we obtain these exogenous cannabinoids? Both CBD and THC both come from the plant family – Cannabis sativa. Within this family you have marijuana and hemp. They are different plants with different amounts of THC 12 .

Marijuana contains anywhere from 3-20% of THC and is used for both recreational and medicinal purposes 12 . Recreational marijuana has a higher amount of THC, eliciting the “high” effect, whereas medical marijuana has a lower amount of THC.

Hemp, on the other hand, contains a very low amount of THC ( 13 . Hemp is no longer associated with negative public effects or with abuse potential.

Hemp vs Marijuana
Hemp Marijuana/Cannabis
Grows up to 20 ft (outside) Grows 6-9 ft (inside)
Harvest 60-90 days Harvest 120 days
Mainly CBD, very low THC (< 0.3%) CBD & THC (3-20%)
No psychoactive effect Psychoactive effect
Uses: Textiles and Health Uses: Recreational and Medicinal

Studies on Cannabinoids and Pain

There are a number of studies correlating cannabinoids and pain relief. The Journal of the American Medical Association reviewed 28 randomized clinical trials and concluded that cannabis therapy for marked pain relief is supported by high-quality evidence 14 . The National Academies of Sciences, Engineering and Medicine found conclusive and substantial evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults 15 . One study in the European Journal of Pain found administration of CBD had long-lasting therapeutic effects on arthritis symptoms without psychoactive side effects 16 . Another study in the Journal of Experimental Medicine found strong evidence suggesting CBD alleviates chronic inflammatory pain 17 . These studies are significant because they suggest cannabinoids offer a viable and a more natural option for pain relief.

Opioid Crisis

Since the 1990s, the prevalence of chronic pain and health care costs have exploded and an opioid epidemic with adverse consequences has escalated. Patients have consumed opioid drugs for pain relief on a massive scale. Considering their potential for tolerance, abuse, and death from overdose, the overuse of opioids form an urgent threat to public health in the USA 18 .

Cannabinoids and Opioid Reduction

Cannabinoids can potentially help with the opioid crisis. States with medical cannabis laws have a 24.8% lower number of deaths from opioid overdose 19 . The number of Medicare prescriptions for drugs to treat pain was reduced in medical cannabis states 19 . In Michigan, there was a 64% decrease in opioid use, a decrease in side effects, and an overall improved quality of life in those who used cannabinoids 19 . Cannabinoids can potentially be used as an alternative or adjunct to opioids and other pain medications.

Addressing Pain through the ECS

There are options available for addressing pain through the ECS.

Hemp-derived CBD

Currently, there is an abundance of hemp-derived CBD products available on the U.S. market. CBD products can be either full spectrum or isolates of CBD. Full spectrum CBD products contain whole plant extract. One study showed that full spectrum CBD oil is superior to an isolate in the effective treatment of inflammatory conditions 20 . Hemp-derived CBD products are currently not federally regulated. A study in the Journal of the American Medical Association found that 70% of CBD products do not match their label 21 . Guidance by a healthcare professional is recommended to determine which product is best for a patient.

Medical Cannabis

Cannabis is approved for medical use in a number of states. Each state has their own specific guidelines for dispensing and prescribing medical cannabis. In Illinois, the Compassionate Use of Medical Cannabis Pilot Program was initiated in 2016. Patients with certain qualifying medical conditions could be certified to obtain a medical cannabis card. In response to the opioid crisis, the Opioid Alternative Pilot Program became available in 2018 and patients could be certified to use medical cannabis for pain relief.

I have found in my own practice that cannabinoid therapy can be effective for the treatment of chronic pain and the response is patient dependent. Chronic pain is a complex condition that is multifactorial and involves multiple body systems. Cannabinoid therapy is one tool that can address pain but best used in conjunction with an integrative medicine approach.

The endocannabinoid system: Essential and mysterious

Many of us have heard of some of the transmitter systems within our bodies, such as the sympathetic nervous system, which gives us our fight-or-flight response. Fewer have heard of the more recently discovered endocannabinoid system (ECS), which is amazing when you consider that the ECS is critical for almost every aspect of our moment-to-moment functioning. The ECS regulates and controls many of our most critical bodily functions such as learning and memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune responses, and eating. The ECS is currently at the center of renewed international research and drug development.

What is the ECS?

The ECS comprises a vast network of chemical signals and cellular receptors that are densely packed throughout our brains and bodies. The “cannabinoid” receptors in the brain — the CB1 receptors — outnumber many of the other receptor types on the brain. They act like traffic cops to control the levels and activity of most of the other neurotransmitters. This is how they regulate things: by immediate feedback, turning up or down the activity of whichever system needs to be adjusted, whether that is hunger, temperature, or alertness.

To stimulate these receptors, our bodies produce molecules called endocannabinoids, which have a structural similarity to molecules in the cannabis plant. The first endocannabinoid that was discovered was named anandamide after the Sanskrit word ananda for bliss. All of us have tiny cannabis-like molecules floating around in our brains. The cannabis plant, which humans have been using for about 5,000 years, essentially works its effect by hijacking this ancient cellular machinery.

A second type of cannabinoid receptor, the CB2 receptor, exists mostly in our immune tissues and is critical to helping control our immune functioning, and it plays a role in modulating intestinal inflammation, contraction, and pain in inflammatory bowel conditions. CB2 receptors are particularly exciting targets of drug development because they don’t cause the high associated with cannabis that stimulating the CB1 receptors does (which is often an unwanted side effect).

The ECS’s role in learning and memory

We know that the ECS plays a critical role in learning and memory due to several lines of research. The most obvious observation is that one of the main side effects of high dosages of recreational cannabis use is the temporary disruption of short-term memory. Memory returns to normal with abstinence. There have also been some sophisticated studies of how humans acutely respond to the administration of THC (the active ingredient in cannabis) and the ways in which this alters both their ability to memorize things in the short term and the patterns observed on their functional brain imaging.

According to the popular writer Michael Pollan in his bestselling book The Botany of Desire, cannabis is one of the plants that humans have cultivated, or co-evolved with, for thousands of years. This is in part, Pollan writes, because the act of forgetting plays a valuable role in the ability of our brains to function without being overloaded with data from our senses that we are continually bombarded with. Pollan hypothesizes that if we didn’t forget, we wouldn’t function, and cannabis helps us do this. The role that the ECS plays in forgetting also opens up opportunities for the treatment of PTSD, a condition in which there are unpleasant, intrusive memories that people can’t help but remember, and that cause a whole syndrome of troublesome and dangerous symptoms related to the pathological remembering.

The ECS’s role in hunger and fine-tuning weight-loss medications

The cautionary tale of the drug rimonabant, a drug that blocks the CB1 receptor, is an interesting example of the central role the ECS plays in so many crucial functions. It was developed as an anti-obesity drug. The thinking was that the ECS controls hunger. We know this because, among other lines of evidence, cannabis gives you “the munchies,” so if you block the CB1 receptor it should cause weight loss. Rimonabant did cause weight loss, quite successfully. But, because the ECS also regulates mood, it had to be withdrawn from the market on an emergency basis because people who were taking it were becoming suicidal. However, we can imagine a case, as we better understand the complexities of the ECS, where we may be able to create a weight-loss medication that acts on those cannabinoid receptors that affect weight loss, but that doesn’t act on those receptors that control mood.

Exploration of the ECS may lead to new drug discoveries

Study of the ECS was initially focused on attempts to understand (and demonize) an illegal drug, but new research has since flourished into a far more broad-based exploration into what is an astoundingly intricate and far-reaching system by which our bodies learn, feel, motivate, and keep themselves in balance. We are truly at the dawn of an age of discovery of the ECS and the development of new medicines that may help alleviate some of the cruelest diseases that people (and animals) suffer from. I am incredibly excited to see what discoveries await us as we continue to untangle the mysteries of the ECS.