The First Family of Cannabinoid Medicine: The Knox Docs

Presentations and panel discussions with the Knox Family are always the highlight of every cannabis science event. For this installment of “Cannabis Crossroads,” I interviewed these true pioneers and leaders of endocannabinology—the Knox Family. This amazing family of four doctors are key opinion leaders in cannabis therapeutics and cannabinoid medicine. Collectively, they have counseled thousands of patients and dedicate time to educating many more by way of talks, seminars, blogs, and videos. 

Q: It is amazing to me that the Knox family not only has four medical doctors, but that all of you are deeply involved with cannabis medicine. How did this come to be?

A: Dr. Janice 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 was open to trying that. Subsequently, after hearing her experiences with the patients in the clinic, Dr. David also had the opportunity to begin seeing patients in the same clinics, while still a full time emergency physician. 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 initially had. 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 for us to pursue the research and science about cannabis and the discovery of the endocannabinoid system (ECS). At that time, Drs. Rachel and Jessica were completing their residency training in family medicine and preventative medicine, respectively. Dr. Janice, especially, talked with them extensively about her experiences with cannabis patients, and piqued their interest in the field. As they were always interested in a more holistic care model than that of conventional medicine, they quickly got on board with learning about the ECS and cannabis therapeutics.

Q: It has frequently been stated that students training to become medical doctors have learned almost nothing about the ECS in the past. In a previous column I wrote about the University of Maryland School of Pharmacy offering a master's degree in medical cannabis science and therapeutics. Is endocannabinology being positively embraced by the medical community? What challenges remain in educating more physicians about cannabinoid medicine?

A: Very few medical training institutions are yet teaching about the ECS, especially as to the fully understood extent and complexities of the system (and the endocannabinoidome). A recent count was that only 13% of medical schools in the US mention the ECS somewhere in their curricula. This is beginning to change as attitudes evolve, even though the legality at the national level has not. Several schools are now offering more extensive courses such as the University of Maryland, but notably these are more likely to be associated with schools of pharmacy rather than medical schools. Younger physicians are, however, more open to accepting the science and institutions are opening up to doing more studies, but we don’t think this is to the point of the mainstream medical community embracing endocannabinology. The challenge is still to do away with a lot of antiquated attitudes (stigma) about cannabis, and to let the science of the ECS and pharmacology of the plant be heard. In some ways, when considering all of the complexities of the ECS and the endocannabinoidome, and the equally convoluting variables in cannabinoid profiles, the average physician just hasn’t had time to figure out what to do with it yet, let alone the institutions figuring out how to teach it. This doesn’t excuse academic institutions of the responsibility to teach their students about the ECS, however. Arguably, it’s not only their due diligence, but a moral obligation to do so given that 100% of patients have one, that all bodily systems are regulated by it, and that cannabis use is increasing significantly across the US population. Failing to teach the ECS is failing to prepare students for the real world.

Q: You must be approached frequently by physicians or students that would like to get more involved in cannabinoid medicine. What advice do you give them?

A: We teach them how fundamental learning the science of the ECS is, and recommend that they begin their education there. Applying the science and pharmacology of cannabis comes more easily with that foundation in place. Understanding and practicing cannabinoid medicine is about so much more than just cannabis. The underlying physiology of the ECS explains why and in what ways cannabis is effective (or sometimes ineffective), but that is only part of the story.

Q: "Ancient Healing" and "Revolutionary Care" are two of the three tenants listed on your website, DoctorsKnow.com. As medical technology advances, do cultures preserve their ancient knowledge, or is much of it lost as attention turns to the development of new drugs and treatments? Have we preserved our ancient healing knowledge or has much of it been lost over time?

A: Our modern approach to medicine, unfortunately, has not retained a lot of ancient wisdom that still exists in what are now looked upon as “alternative” medicine fields, including naturopathy, ayurvedic medicine, Chinese medicine, and acupuncture—and probably by design. We’ve even coined them “alternative,” when the real alter (counter-to) native (natural) medicine is conventional, Western medicine. So there is some acknowledgment of those areas, but always as inferior to the power of conventional medicine.

Cannabis itself was displaced from a level of prominent use until less than 100 years ago, by the introduction of more specific monomolecular pharmaceuticals as well as by the political machinations to outlaw the plant. This deliberate act to remove cannabis from the pharmacopoeia and severely limit any study on the plant certainly resulted in a loss of knowledge, and a loss of at least two generations of research that could have been so helpful to so many. Much has been lost in terms of the broad education of medical practitioners in general, although the knowledge can still be found in smaller arenas. The understanding of the ECS is helping to support why many ancient and alternative practices have efficacy, and we hope will contribute to a new awakening of integrating all methods toward better health for all.

Q: What is "integrative cannabinology"? What is most important for our readers to know about this field?

The Knox Docs presenting at the 2019 Cannabis Science Conference West. Photo credit: @Cannakopiaorg

A: Functional and integrative endocannabinology is the application of functional and integrative medicine practices to correct endocannabinoid dysfunctions (and thus disease) at their root cause. Several common and difficult to treat conditions—such as migraines, fibromyalgia, post-traumatic stress disorder (PTSD), epilepsy, and obesity among others—have been associated with ECS dysfunction. The functional piece of endocannabinology means that rather than treating only the symptoms of these conditions, we seek to correct the underlying endocannabinoid dysfunction—the root cause. The integrative piece means we address the symptoms and root cause with a combination of treatment modalities, including not only cannabis, but also nutrition, cannabimimetic substances and practices (for example, herbs, spices, terpenes, mind-body therapies, exercise), and even conventional therapies when appropriate. This is a burgeoning field of medicine that we believe all clinicians should know something about, and that we hope will become a board-certified specialty or subspecialty in its own right in the near future.

Q: In very recent history we have witnessed an opiate crisis that has had a devastating impact on our families and communities. The very people seeking freedom from chronic pain were suddenly snared in a deadly addiction trap that robbed everything from their life. How important is cannabis and other natural medicines in allowing people to break their opiate addiction and what has the medical community learned from this disaster?

A: The current opioid catastrophe resulted when big pharma seeking big money pushed their pharmaceuticals to expand their market. The push to define pain as the “5th vital sign” and the declaration that pain was not being adequately treated, plus the questionable studies that opioids were not addicting for true pain patients, allowed for the huge increase of opioids available to everyone. It can be extremely difficult to distinguish between a patient with legitimate pain, especially chronic pain, and those simply needing the opiate to stave off withdrawal. The current push to limit opioids for everyone now results in denial of relief for those truly needing opioids for pain management. In many cases, this results in practitioners treating the policies rather than the patient. I’m not sure the medical community as a whole has learned much, rather that this is just the swing of the pendulum we operate under.

Cannabis and other integrative modalities, on the other hand, do have a lot to offer for pain management and opiate addiction. The anecdotal attestation from thousands of our patients that they were able to reduce or eliminate the need for opioids for their chronic pain conditions is astoundingly important, even if some controlled studies that have been published do not prove this with a statistically significant difference. Many patients do get pain relief from cannabis alone, and studies show the synergism of cannabis with opioids. This means that with cannabis use the patients get better pain relief from a lower dose of opioids, and do not develop the same increasing tolerance and need for a higher opiate dose over time. This lowers the risk associated with treatment with opioids such as respiratory depression and even death. The fact is that pain relief from cannabis does not require any level of intoxication from THC. We can’t count the number of patients who state emphatically that cannabis saved their lives from opioids.

Unfortunately, in the national forums on the opiate crisis, there have been many subjects discussed but minimal, if any, mention of cannabis or of other natural medicines, such as kratom. This is likely due to no US Food and Drug Administration (FDA) approval of any of these other modalities.

Q: Pharmaceutical companies have embraced biotherapeutics, but there still seems to be a heavy focus on isolating a single, bioactive component and developing this single component drug to market. Medical cannabis and whole plant medicine is the antithesis of this approach and patients benefit from the synergistic action of many plant compounds (cannabinoids, terpenes, bioflavonoids). Is the isolation of a single component by pharma companies a failed strategy? How do we bridge the gap between these pharma approaches and nutraceuticals?

A: It is hard to call it a completely failed strategy, as the FDA approval of Epidiolex (essentially a CBD isolate) resulted from this approach by GW Pharmaceuticals. This does highlight the difficulties of studying the effects of a complex polypharmaceutical represented by the whole plant versus a single molecule. This is like multivariable calculus versus linear addition or subtraction, and does not lend itself amenable to the double blinded controlled studies the FDA and pharmaceutical developers require for approval. That system is designed to work with isolates, but as we know, the entourage effect is much more powerful. Epidiolex works, with a significant benefit in reducing seizures, but often requires precise and higher doses with more risk of side effects; whole plant extracts with the full entourage work better, at a much lower dose of CBD. The entire interplay of all the cannabinoids, terpenes, and other components carries a lower risk of side effects. Studying complex plant medicines would require a change in the fundamental approach taken by the FDA to conduct research. The agency would need to broaden its focus on isolates as pharmaceutical drugs to include whole plant, nutraceutical research.

When you look at the history and spectrum of cannabis use, with its remarkable safety profile compared to most pharmaceuticals, there is no reason that whole plant cannabis needs to be subject to that same level of controlled study. While inexact for actual dosing, the approach of time and titration of the cannabis profile (CBD:THC amounts and ratios, other cannabinoids, terpenes, and flavonoids present) has been effective for multitudes of people for millennia. We hope that this approach can be refined to be more exact for any individual patient, but including cannabis as part of one’s approach to health and lifestyle is very low risk, and the FDA needs to realize this.

Q: There seems to be a shift in healthcare—a moving away from reactive treatment towards more proactive health and lifestyle management. Is medicine moving from disease treatment to disease prevention?

A: On one hand, much of our modern medical approach to treatment is in reaction to illness or injury. This is necessary to help patients recover and regain their life, but has not been very effective in resolving or controlling many chronic disease processes. Medicine has always had a niche for preventive medicine, but it does not yet seem to be a big movement in the medical establishment. Many people are realizing this, and that they individually need to be much more proactive in managing all those elements in their lifestyle that contribute to the risk of developing or managing those chronic medical conditions. This includes everything from diet and nutrition, exercise and activity, family and relationships, to chemical and toxic exposures. Our current Western approach really is poorly designed for that, as overall health is so dependent on the entire environment we are living in 24/7/365. You see your doctor for 10 minutes, who may refer you out for dietary counseling, physical therapy or exercise, other programs such as smoking cessation and so forth, but these are piecemeal approaches in many cases. Where you live can be a huge factor if you have limited access to clean water, healthy food choices, and the ability to exercise. We talk about health equity, but that cannot be separated from systemic, total equity, something we call “health equity.”

Q: We are learning so much more about cannabis. What are you most excited about regarding cannabinoid medicine?

A: We believe there will be a renaissance in the clinical studies needed to bring cannabinoid medicine into the forefront. The science of endocannabinology will continue to develop and explore the workings of the complex physiology of the endocannabinoidome. The lack of well-designed clinical studies (the reasons why we’ve already discussed) on the use of cannabinoid therapeutics has been the limiting factor for most physicians to ignore or downplay any role for incorporating cannabinoids into their practice. With the increased acceptance of cannabis, we hope the path will be cleared and this research can move ahead. Already there are proposals to study the use of CBD or other cannabinoids in the treatment of COVID-19, especially those patients suffering a cytokine storm, the hyperinflammatory reaction that causes severe illness. High profile studies such as that may be the impetus to allow for even more clinical studies on the myriad of conditions we know cannabinoids can help.

About the Interviewees

Dr. Jessica Knox received her bachelor’s degree from Harvard University before going on to earn her medical and business degrees from Tufts University. She completed her postgraduate training in Preventive Medicine at the University of California San Diego while earning her public health degree from San Diego State University. Dr. Jessica believes that using all-natural remedies to fight disease and promote well-being should be the first-line approach in medical care. With healthcare costs soaring, and access to medical care as limited as ever, she believes the application of lifestyle and natural medicine is key to adequately addressing the current state of public health in our communities and country as a whole. It was out of this belief that Dr. Jessica’s interest in cannabis therapeutics blossomed.

Dr. Janice Marie Vaughn Knox has more than 35 years in the practice of medicine. She is a graduate of the University of California at Berkeley and the University of Washington School of Medicine. She is a wife, mother, best selling author, and board certified anesthesiologist. Over her years in the operating room, Dr. Janice witnessed the increased use of life threatening pain medications and unnecessary medical interventions that yield low success rates while patients continued to get sicker. This awareness motivated Dr. Janice to become an expert in cannabis and the fields of cannabis therapeutics and endocannabinology.

Dr. David Knox is a graduate of the University of Washington and University of Washington School of Medicine. After 37 years of clinical experience in emergency medicine and counting, he has expanded his expertise to include cannabis therapeutics. Dr. David has consulted with more than 5000 patients across the Pacific Northwest within the past year, noting the degree of results cannabis has had on a variety of maladies, but perhaps none more common than chronic pain, a condition which plagues emergency rooms nationwide.

Dr. Rachel Knox received her medical and business degrees from Tufts University after completing her undergraduate studies at Duke. She trained in family and integrative medicine before pursuing additional study in the areas of functional, cannabinoid, and cannabis medicine. Though her formal training in family and integrative medicine provides her with the know-how to treat acute illness and chronic disease, she is passionate about teaching her patients how to avoid and even reverse them altogether through natural means.

ABOUT THE COLUMNIST

JOSHUA CROSSNEY is the columnist and editor of “Cannabis Crossroads” and a contributing editor to Cannabis Science and Technology magazine. Crossney is also the president and CEO of CSC Events. Direct correspondence to: Josh@CannabisScienceConference.com

How to Cite this Article

J. Crossney, Cannabis Science and Technology 3(6), 22-23 (2020).