Understanding Cannabinoids and Their Role in the Endocannabinoid System (ECS)

Cannabinoids are fascinating chemical compounds that interact directly with the body’s endocannabinoid system (ECS) — an essential network that helps regulate many physiological processes like mood, sleep, pain perception, and more. The body produces its own cannabinoids in the form of endocannabinoids. By contrast, phytocannabinoids are produced by the cannabis plant - more on this later. In addition to the major phytocannabinoids, Δ9-THC (often referred to as THC) and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor cannabinoids. These cannabinoids are produced in smaller amounts in the plant.

This blog will explore the ECS, the differences between major and minor phytocannabinoids, and discuss how these cannabinoids work to promote balance and well-being in the body. Whether you're new to medical cannabis or looking to deepen your knowledge, let's break down the essentials.

What Is the Endocannabinoid System (ECS)?

The ECS is a biological system made up of three principle elements:

1. Endocannabinoids - Naturally occurring cannabinoids in your body, like anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These interact with receptors and are produced on demand to maintain internal balance.

2. Receptors - Two main types, CB1 and CB2, are found throughout the body. CB1 receptors are concentrated in the brain and nervous system, influencing pain, memory, and mood. CB2 receptors reside in peripheral tissues and immune cells, often regulating inflammation and immune responses. Cannabinoid interactions extend beyond the CB1 and CB2 receptors but for the purposes of this blog we will limit our discussion to CB1 and CB2 receptors.

3. Enzymes - These break down endocannabinoids after they've fulfilled their function to prevent overactivity.

The ECS is a regulatory system found within all complex animals. It regulates such diverse functions as memory, digestion, motor function, immune response and inflammation, appetite, pain, blood pressure, and the protection of neural tissues, among others. Endocannabinoids appear to be profoundly connected with the concept of homeostasis and help to redress imbalances presented by disease or by injury.

Phytocannabinoids and the ECS

As previously noted, the body produces its own cannabinoids in the form of endocannabinoids. By contrast, phytocannabinoids are produced by the cannabis plant in the form of carboxylic acids: THCA, CBDA, and so on. Upon heating these phytocannabinoid acids are converted to their chemically neutral and more widely known forms: THC, CBD, etc., through a process called decarboxylation. Phytocannabinoids interact with the ECS by binding to its receptors.

The Diversity of Cannabinoids

The cannabis plant produces over 120 cannabinoids, but they fall into two main categories:

1. Major Cannabinoids

• THC (tetrahydrocannabinol) binds primarily to CB1 receptors, producing psychoactive effects, pain relief, and appetite stimulation. Though CB1 receptors are concentrated in the brain and nervous system they are not significantly expressed in the brain stem which is responsible for respiration and circulation. This is a primary reason why cannabis overdose does not cause respiratory depression and death, both of which are possible with opioid overdose.

• CBD influences the ECS differently. Instead of binding directly, it may boost the body's natural production of endocannabinoids by slowing their breakdown. It is non-intoxicating and often used for its purported anti-inflammatory, anxiolytic, and neuroprotective properties.

2. Minor Cannabinoids

Often found in smaller concentrations, these compounds are gaining attention for their unique benefits. Emerging evidence suggests that minor cannabinoids like cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC) and tetrahydrocannabivarin (THCV) also play significant roles in the ECS. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders.

• CBG (Cannabigerol) is referred to as the "mother cannabinoid" because it’s the precursor for other cannabinoids like THC and CBD. Research suggests it may aid in reducing inflammation and stimulating appetite. CBG has shown some promise suppressing cancer cell growth but clinical studies are needed to determine if the results are translatable to treatment in humans.

• CBN (Cannabinol) is not synthesized in the cannabis plant, but is derived during the degradation of Δ9-THC. CBN has been identified as a potential analgesic and anti-inflammatory agent. CBN also shows promise as an antibacterial agent and an appetite stimulant. Though advertised for promoting sleep, controlled studies are warranted to substantiate sleep-related claims of CBN containing products.

• CBC (Cannabichromene) may help reduce pain and inflammation as well as act as a neuroprotective drug. CBC may be beneficial in cancer treatment due its possible anti-tumor effects.

• THCV (Tetrahydrocannabivarin) may help regulate appetite and shows promise for weight management and metabolic health. THCV may also help in reducing inflammation and inflammatory pain.

Preclinical data and early clinical studies support the continued investigation of phytocannabinoids for the treatment of pain, inflammation, neurodegeneration, cancer and other disorders. Minor cannabinoids offer the potential medicinal benefits of Δ9-THC without adverse effects. Clinical trials are needed as much of our current knowledge of the medicinal benefits of minor cannabinoids has come from subjective and anecdotal patient reporting.

The "entourage effect" theorizes that when cannabinoids and other natural compounds in cannabis work together, their combined benefits are amplified compared to using isolated cannabinoids alone. Full-spectrum products that preserve these compounds often harness this synergistic effect.

Safety and Drug Interactions with Cannabinoids

While cannabinoids are generally considered safe, they can interact with medications in unexpected ways. For instance:

• CBD and THC are metabolized by liver enzymes like CYP3A4 and CYP2C9, which are also responsible for breaking down an array of medications, including blood thinners like warfarin.

• A 2019 study highlighted cases where CBD increased the effectiveness of anti-seizure medications like clobazam by slowing its breakdown, leading to potential side effects.

If you are considering cannabinoids for therapeutic purposes, consulting with your medical doctor or healthcare professional is crucial to understand how they might interact with your medications.

Why Explore Medical Cannabis for Wellness?

Over the years, cannabis has shown potential across a range of conditions, from chronic pain and sleep issues to anxiety and immune regulation. Researchers have even started exploring the idea of endocannabinoid deficiency, which may explain why some people respond well to cannabinoid therapy when managing conditions like migraines, fibromyalgia, and irritable bowel syndrome.

Understanding and engaging with the ECS might unlock new approaches to addressing these persistent health struggles, making medical cannabis a valuable option for patients looking for more natural ways to feel better.

Take the Next Step

Connect with ElevateCareNP today to begin your medical cannabis certification process. Discover how the natural benefits of cannabinoids can empower you to take control of your wellness.

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Sources:

1. Grinspoon, P. (2021, August 11). The endocannabinoid system: Essential and mysterious. Harvard Health. https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

2. Walsh, K. B., McKinney, A. E., & Holmes, A. E. (2021, November 29). Minor cannabinoids: Biosynthesis, molecular pharmacology and potential therapeutic uses. Frontiers in pharmacology. https://pmc.ncbi.nlm.nih.gov/articles/PMC8669157/

3. Di Marzo, V., et al. (1998). Endocannabinoids: Endogenous Cannabinoid Receptor Agonists in the Brain and Periphery. Prostaglandins, Leukotrienes, and Essential Fatty Acids.

4. Whiting, P. F., et al. (2015). Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA.

5. Mechoulam, R., Parker, L. A., & Gallily, R. (2002). Cannabidiol: An Overview of Some Pharmacological Aspects. The Journal of Clinical Pharmacology.

6. Russo, E. B. (2011). Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects. British Journal of Pharmacology.

7. Huestis, M. A. (2007). Human Cannabinoid Pharmacokinetics. British Journal of Clinical Pharmacology.

8. Baron, E. P. (2018). Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis and Benefits in Migraine, Headache, and Pain. Headache.

The information in this post is intended for educational purposes only. This information neither substitutes for nor replaces professional legal or medical advice, diagnosis, or treatment. No content on this site should ever be regarded as a substitute for direct medical advice from your doctor or other qualified clinician.