Market Overview

The Endocannabinoid System: 8 Questions With Dr. David Knox

The Endocannabinoid System: 8 Questions With Dr. David Knox

By Stephanie Johnson.

The Endocannabinoid System was discovered in the 1990’s and, ever since, has been a growing field of scientific research. The Doctors Knox, a family of physicians, have been involved in this specialty since they began signing patient authorizations after successful decades in their specialty medical practices. Now they are found speaking throughout the country about the human Endocannabinoid System, what it is, and how cannabis works with it for the betterment of multitudes.

Dr. David Knox was kind enough to spend a few moments to answer some of my questions that I had about the famed ECS. What is it and what exactly do we know about it these days? What kind of possibilities can we expect to see or learn about soon?
Check out his answers to those questions and more in the Q & A below:

Stephanie Johnson: Please, take a moment and tell us about your background into Endocannabinology:

Dr. David Knox: I was a board certified Emergency Physician for 35 years before my introduction to cannabis medicine and the ECS. My wife, Dr. Janice Knox, had been a board certified Anesthesiologist for 32 years before retiring from the operating room. She was invited to work for a Medical Marijuana clinic to sign authorizations for patients to access their cannabis legally, and after her initial experience, I also had the opportunity to see patients in the same clinics. Superficially, it was easy to sign the authorizations, as patients clearly had conditions on the state approved list of qualifying conditions, but this introduction to Cannabis medicine was so eye-opening for us that we had to actively pursue further knowledge.
To start, the patients we were seeing defied any expectation we may have had initially. Our prior exposure to Cannabis in the conventional medical space was that it was simply a drug of abuse. This was quickly disproved, as these were patients from all walks of life, with complex medical histories, who were using Cannabis therapeutically for many reasons but were having better results than any conventional therapies had given them. After a few thousand people give you the same story about Cannabis, you have to listen to what they are saying. This was the impetus to pursue the research and science about Cannabis and the discovery of the Endocannabinoid System. So it has involved a great deal of self study in researching published articles, and trying to put a stronger scientific basis toward the clinical application of cannabinoid therapeutics. It is still astounding that there is so little education about such a fundamental portion of our physiology in medical schools. With the amount of research done in so many areas, it is time that the ECS be brought into conventional medicine, so we are actively trying to change this narrative.

SJ: What about this plant (Cannabis) family most excites you?

Dr. Knox: I am most excited by the amazing versatility of applications for cannabis based products. We are only scratching the surface of therapeutic possibilities with current use and focus on only a few cannabinoids (THC and CBD). Even so, the breadth of medical problems that can be helped is impressive. The multiple variables in the profile of the plant (meaning Cannabinoid amounts and ratios and which dominant terpenes are present) allows a spectrum of applications for any patient and medical problem. Aside from medical application, the many other uses of cannabis for food, fiber, oils, building materials, etc. can have a huge economic impact in all industries.

SJ: When looking at the ECS, what should people beginning to learn about the plant know first?

Dr. Knox: The Endocannabinoid System is named as such because it was discovered using synthetic THC to identify the receptors in the body. The ECS, however, has been found to be the largest signalling system in the body, modulating virtually every other system in some fashion.

The endocannabinoid system is a complex and integral part of our entire physiology. So, while cannabis and phytocannabinoids can have pharmacological effects through the cannabinoid receptors, the ECS itself is really what is important for health. There are many other factors than just Cannabis affecting the ECS, and we talk about cannabimimetic substances and practices that can also influence the ECS.

SJ: People are now learning more about the ECS, and how there are more than just a few receptors involved. How vast is the ECS?

Dr. Knox: The basic ECS is described as the cannabinoid receptors (CB1 and CB2), the endocannabinoid ligands (Anandamide and 2-AG), and the enzymes involved in creating and breaking down the endocannabinoids. Research has uncovered a vast array of other receptors in the cells of the body that are also affected by the endocannabinoids and other lipid signalling molecules, including GPR55, TRPV receptors, PPAR receptors on nuclear membranes, and others. CBD alone has effects on an estimated 65 other receptor types and enzymes, including the opioid receptors. We are talking more about what can be called the Endocannabinoidome which includes all these related signalling molecules and receptors as they are all interconnected.

SJ: CBD is the darling these days, but what other of the minor cannabinoids show potential for medical benefit?

Dr. Knox: CBD has been pushed along as the “non-psychoactive” cannabinoid compared to THC, which is often used for its intoxicating effects. While CBD is not intoxicating as in causing a “high”, it certainly is psychoactive when it helps PTSD, anxiety, and other mood disorders. But this distinction is what allowed CBD to come onto the market legally, while THC is still federally

illegal. The first of the other medically beneficial cannabinoids are THCA and CBDA, the acid forms which are produced in the plant. Heating the cannabinoids causes decarboxylation, the removal of the acid side chain, resulting in neutral THC or CBD. THCA is not intoxicating but still has many of the medical benefits, including anti-inflammation, anti-cancer, and anti-nausea effects. CBDA is even more anti-inflammatory than CBD for some conditions like inflammatory bowel disease. CBGA is the mother cannabinoid in the plant, and usually is converted to CBDA and THCA through separate enzymatic pathways, but strains now being grown retain high concentrations of CBGA’s neutral derivative, CBG.

While there is still very little study of CBG (or the other minor cannabinoids) compared to THC and CBD, preliminary indications are that CBG will have major medical benefits. CBG also is non-intoxicating, and is more of a blocker at CB1 whereas THC stimulates CB1 to cause intoxicating effects. CBN is a breakdown product of THC, and may be helpful for sleep, although that effect may be due to sesquiterpenes in the aged plant material. THCV and CBDV are variants with a 3-carbon side chain rather than a 5-carbon side chain, and both have been found to be medically beneficial; again THCV has perhaps 10% of the intoxicating effect of THC. Research will continue to delineate benefits of other cannabinoids, including CBC (cannabichromene), and other cannabinoids that are still being discovered.

SJ: Can you describe the entourage effect?

Dr. Knox: The entourage effect is a term used to describe the increased or improved effect of a combination of molecules working together, resulting in an effect greater than the simple sum of each component individually. Synergy is a similar term, where combining two or more components results in an increased benefit compared to using each one alone. This may be due to the influence of the separate components on the same receptors, or by working through separate pathways entirely to achieve the same result. This is clearly demonstrated in studies that have been done with Epidiolex, which is essentially a CBD isolate. Patients have had improved seizure control with Epidiolex, but have often required fairly high doses to accomplish that. When CBD is accompanied by the other cannabinoids, terpenes, and flavonoids present in the whole plant, patients get better results (improved efficacy) with lower doses of CBD, as low as one quarter the amount of CBD as required with the CBD isolate. CBD often works better when combined with some THC, and linalool is an important terpene that also has some anti-seizure effect itself.

SJ: What do you see coming down the pike, as new products and innovations?

Dr. Knox: As the industry evolves, we are seeing new product lines introduced, such as inhalers using the same aerosol devices as for bronchodilators, dissolvable oral strips, transdermal patches and other delivery methods that can provide medical benefit without smoking. Manufacturers will broaden the use of more of the minor cannabinoids and we are already seeing oils and tinctures using more of the acid cannabinoids and CBG. Noting the importance of the terpenes along with the cannabinoids, I am hoping there will be more emphasis on testing and listing the terpene contents of cannabis products for the consumer.

SJ: How can people keep up with your work?
Dr Knox: We can be followed through our website,, and on Instagram @theknoxdocs.

From The First Family of Cannabinoid Medicine - The Knox Docs are a family of physicians with backgrounds in Emergency Medicine, Anesthesia, Family Medicine, Integrative Medicine, and Preventive Medicine. They have expanded their expertise to include Integrative Cannabinology, Functional Endocannabinology and Cannabinoid Medicine, and are internationally recognized as thought leaders in the care of the endocannabinoid system and cannabis therapeutics. From cannabinoid science and patient care, to cannabis regulation, the Knox Docs boast a wide range of interests, involvement, and experience.

Stephanie Johnson is a writer and content creator who is a part of the Research and Informative Content team at The Skyline Agency in Dallas, Texas. Specializing in lifestyle, wellness, and beauty, Johnson has contributed to a multitude of publications throughout her over 15 years of experience in multiple forms of media.

The preceding article is from one of our external contributors. It does not represent the opinion of Benzinga and has not been edited.

Lead image by Ilona Szentivanyi. Copyright: Benzinga.


Related Articles

View Comments and Join the Discussion!

Posted-In: Dr. David Knox endocannabinoid system Stephanie JohnsonCannabis News Markets Interview