An overview of our endocannabinoid system, its correlation to chronic pain and available treatment options.
By Rowena Chua, MD
June 17, 2019
Systems of the Body now include The ECS. (Click to enlarge)
Cannabis is a plant-based product that has been used medicinally for at least 4,000 years1. 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 highs2. 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 discovery3.
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 balance4. Important components of the ECS are cannabinoid receptors and endogenous cannabinoids.
Cannabinoid Receptors: CB1and CB2
Located throughout the body, cannabinoid receptors are part of our ECS. There are 2 main cannabinoid receptors: CB1and CB2. CB1receptors are found predominantly in the brain, while CB2receptors are mostly found in the immune system5. 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.
Cannabinoid Receptors: CB1and CB2. (Click to enlarge)
Endogenous Cannabinoids: Anandamide
In 1992, scientists discovered what binds with cannabinoid receptors— Anandamide, one of the cannabinoids that our body produces6. It was named after the Sanskrit word “ananda” meaning “bliss”. It’s found to be directly correlated with improved mood, reduction of depression and anxiety7.
The ECS regulates a host of physiological processes including mood, memory, appetite, muscle control, immune function, inflammation, as well as pain levels8.
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 conditions9. 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 it with plant cannabinoids. The 2 main exogenous or plant cannabinoids are CBD and THC.
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 psychosis10.
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 CBD10. 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 CBD11.
CBD vs THC
|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 THC12.
Marijuana contains anywhere from 3-20% of THC and is used for both recreational and medicinal purposes12. 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 (<0.3%). Unlike marijuana, it consists mainly of CBD with no psychoactive effect. Prior to December 2018, hemp was considered a controlled substance like marijuana. The passing of the 2018 Farm Bill permanently removed hemp-derived cannabinoids from the Controlled Substances Act13. Hemp is no longer associated with negative public effects or with abuse potential.
Hemp vs Marijuana
|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 evidence14. 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 adults15. One study in the European Journal of Pain found administration of CBD had long-lasting therapeutic effects on arthritis symptoms without psychoactive side effects16. Another study in the Journal of Experimental Medicine found strong evidence suggesting CBD alleviates chronic inflammatory pain17. These studies are significant because they suggest cannabinoids offer a viable and a more natural option for pain relief.
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 USA18.
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 overdose19. The number of Medicare prescriptions for drugs to treat pain was reduced in medical cannabis states19. 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 cannabinoids19. 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.
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 conditions20. 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 label21. Guidance by a healthcare professional is recommended to determine which product is best for a patient.
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.
- Zias J, Stark H, Sellgman J, Levy R, Werker E, Breuer A, Mechoulam R. Early medical use of cannabis. Nature. 1993 May 20; 363(6426):215.
- McCarthy, Justin. Two in Three Americans Now Support Legalizing Marijuana. Gallup. 2018 October 22.News.gallup.com.
- Pertwee, R. (2006). Cannabinoid pharmacology: the first 66 years. British Journal of Pharmacology, 147 (Suppl 1), 163-171.
- Sallaberry C, Astern L. The endocannabinoid system, our universal regulator. Journal of Young Investigators. June 2019; 34 (6): 48-55.
- Pacher P, Mechoulam R (2011). “Is lipid signaling through cannabinoid 2 receptors part of a protective system?”. Prog Lipid Res. 50 (2): 193–211. doi:10.1016/j.plipres.2011.01.001. PMC 3062638. PMID 21295074.
- Devane, W.; Hanus, L; Breuer, A; Pertwee, R.; Stevenson, L.; Griffin, G; Gibson, D; Mandelbaum, A; Etinger, A; Mechoulam, R (18 December 1992). “Isolation and structure of a brain constituent that binds to the cannabinoid receptor”. Science. 258 (5090): 1946–1949. Bibcode:1992Sci…258.1946D. doi:10.1126/science.1470919. PMID 1470919.
- Stone NL, Millar SA, Herrod PJJ, et al. An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers. Front Behav Neurosci. 2018;12:269. Published 2018 Nov 26. doi:10.3389/fnbeh.2018.00269.
- Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A (January 2017). “Targeting the endocannabinoid system: future therapeutic strategies”. Drug Discovery Today. 22 (1): 105–110. doi:10.1016/j.drudis.2016.08.005. PMID 27554802.
- Russo, EB (2004). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions. Neuro Endocrinology Letters, 25(1-2), 31-39.
- Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2(6):241–254.
- World Health Organization, & WHO Expert Committee on Drug Dependence. (March 2018). WHO Expert Committee on Drug Dependence: thirty-ninth report.
- Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci. 2016;7:19. Published 2016 Feb 4.
- Monke, Jim (May 31, 2018). Farm Bills: Major Legislative Actions, 1965-2018 (PDF). Washington, DC: Congressional Research Service. Retrieved 14 June 2018.
- Whiting, PF, et. al.(2015). Cannabinoids for Medical Use A Systematic Review and Meta-Analysis. JAMA, 313 (24): 2456-2473.
- National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: Current state of evidence and recommendations for research. Washington, DC: The National Academies Press.
- Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936–948. doi:10.1002/ejp.818.
- Xiong W, Cui T, Cheng K, et al. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med. 2012;209(6):1121–1134. doi:10.1084/jem.20120242.
- Bolliger L, Stevens H. From Opioid Pain Management to Opioid Crisis in the USA: How Can Public-Private Partnerships Help?. Front Med (Lausanne). 2019;6:106. Published 2019 May 14.
- Boehnke, KF et. al. (2016) Medical Cannabis Use is Associated with Decreased Opiate Medical Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain. The Journal of Pain: official journal of the American Pain Society,17(6): 739-44.
- 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.
- Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017;318(17):1708–1709.