Perspectives on CBD Pharmacology
Feb/March 2020 CBD Health & Wellness
Cannabinoids are wonderful compounds with one very big problem–they are lipophilic, or fat loving.[1] This makes dosing very, very tricky and is also why it’s so hard to measure cannabinoid levels in the blood and urine. The pharmacokinetics and pharmacodynamics of cannabinoids are greatly affected by various factors, such as the amount and type of food eaten in a given day, whether other substances, including medications, were taken, and how they were consumed (vape, oils, edibles, etc.).[1] For these reasons and more, the best advice to offer new users remains the “start low, go slow” method, which is as unscientific as it comes. And explains why this topic remains red hot in research.
Recently, the European Union designated cannabidiol (CBD) as a “novel food,” while the former chief regulator at the US Food and Drug Adminsitration (FDA), Scott Gottlieb, was quoted around the same time saying that CBD is “not safe,” demonstrating a conflicted international perspective toward a rapidly emerging market.[2,3] Additionally, research into cannabinoids is significantly restricted, with the greatest detriment being clinicians and consumers who are left confused by a lack of guidance on many crucial issues related to best practices surrounding CBD.
At CBD Expo East this past November, experts from across industries met to explore some of these topics in earnest during a panel discussion on Cannabinoid Pharmacology. This panel featured Cohin Kakar, PharmD, MBA, Chief Marketing Officer of the Anthos Group; Adam Abodeely, MD, MBA, FACS, FASCRS, Founder of ReserveMD; William Fisher, Chairman of Diverse Biotech, Inc.; and William Taylor, MD, CEO of Integrated Hemp Solutions. Speaking to a diverse room of consumers, as well as a number of CBD manufacturers, caregivers, and researchers, they discussed an array of topics, including the basic pharmacology of CBD, the endocannabinoid system (ECS) and inflammation, the role of various cannabinoid delivery systems, developments in CBD supplements and biopharmaceuticals, and the future of genetics, the entourage effect, and personalized medicine.
Starting the panel off, Dr. Abodeely drew on his multi-disciplinary background to eloquently lay out a summary of what we know about CBD basics. CBD in dosages as high as 1500 mg/day are well tolerated, despite a recent publication claiming it causes liver toxicity; as most consumer-level dosages fall well below those referenced in the study, hepatic effects should not be a major concern for most.[4] Noting legitimate issues surrounding drug interactions and comorbidities, Dr. Abodeely personally has yet to see these in his own practice.
CBD, Dr. Taylor elaborated, is “not a drug”–although it is an ingredient in Epidiolex® and other pharmaceuticals in development–and that consumers use this product for diverse reasons. He also pointed out how, in the context of all pharmaceuticals, there is always a question of interactions and that the importance of consulting a physician for any kind of cannabis treatment cannot be overstated. Mr. Fisher took the opportunity to discuss the potential for cannabis to streamline therapies, referencing the work his firm is doing toward improving chemotherapy medications. In both cases, the potential for cannabis to make treatments more efficient and effective was a sentiment shared by the panel and echoed by Dr. Abodeely who talked about the importance of retailers and manufacturers working with physicians in developing products, treatments, and programs for consumers. Altogether, the panel seemed confident that cannabis-based products, particularly CBD, were an inevitable and evolving part of the health and wellness landscape and that the science of safety will eventually catch up with consumer demand for access.
The panel was also in agreement about the great potential of cannabinoids to treat inflammation, both in terms of drug development and improving patient outcomes. Mr. Kakar felt that better understanding disease pathways and the role of inflammation will aid in the development of better drugs, while Dr. Taylor explained that the intersection of inflammation with other bodily systems will create more robust frameworks that focus on global health. Mr. Kakar continued by raising the potential of the entourage effect and the potential modulatory effects of cannabis beyond the ECS.
As cannabis affects the whole body, the ECS is part of whole body homeostasis, added Dr. Aboodeely. As an internal physician, Dr. Taylor continued, triaging the ECS allows for a better treatment plan rather than chasing symptoms. Indeed, the idea of endocannabinoid deficiency as a significant concept was agreed upon by the panel, while Mr. Kakar and Mr. Fisher alluded to the potential insights that understanding how the entourage effect and ECS operate may faciliate cancer treatment. At the present, however, traditional wellness represents the extent of what is accessible to consumers.
Different delivery systems have different effects, and there is no one-size-fits-all approach to developing cannabis treatments. Even as regulations slow science, our tools for measuring the efficacy of cannabis treatments lags even further. While clinicians and researchers can make focused evidence-based claims, the barriers to researching the plant within institutional settings is daunting. An example of an area with great potential and immense difficulty is the role of cannabis topicals. Not much is known about the long term vs. acute effects of these products, pointed out Dr. Abodeely. In addition, the plant’s entourage effect having a kind of allosteric regulatory potential means that products can work without quite knowing how, pointed out Dr. Taylor. Ultimately, understanding what place CBD and other plant moieties will play in foods, drugs, and supplements is critical, agreed Mr. Kakar and Mr. Fisher.
The future of ECS support or intervention is heavily tied to the regulatory status of the plant. The FDA has signaled a future for CBD that makes a supplement path difficult to impossible, while also decrying the potential benefits of the moiety. Indeed, the FDA is in the business of regulating molecules as drugs and, therefore, products like Epidiolex will ultimately represent the future of CBD drugs argued Dr. Abodeely. However, added Mr. Kakar, CBD can be considered somewhere in between a supplement and a drug, thinking about it like products such as fish oil and vitamins. Drawing on the wisdom of Ethan Russo, MD, Dr. Taylor described full-spectrum oil and nutraceuticals as an integral part of his current practice.
Dr. Taylor also discussed the future of synthetic cannabinoids and the role of pharmaceutical companies in helping propel research and product development. Mr. Kakar agreed that understanding the comparative value of lab-synthesized cannabinoids compared to naturally-derived cannabinoids will be an important part of the regulatory and practical future of cannabis medicine. Whether it is improved cancer treatments, genetic endocannabinoid deficiency tests, or robust analogs, the panel as a whole was optimistic for the future of cannabis medicine despite the current regulatory stranglehold on the industry, stressing the need to move slowly and intentionally to help build consumer trust and develop more robust and targeted treatments. Even as we wait on research, we can still work to educate the public about best practices and dispel myths and stereotypes surrounding the plant, pointed out Dr. Abodeely. As Mr. Fisher elaborated, despite some of the strict limitations the FDA places on what can be said about drugs in development, public education will remain key.
Throughout the conversation, it became evident that the science of cannabinoid pharmacology has progressed rapidly since the advent of hemp and cannabis products in the US; however, our understanding is still lagging. We know that cannabis products work and have theories on where we can apply our current understanding to improve medicine but have a long way to go before realizing the full potential of things like the entourage effect. Despite new developments in drug delivery systems and biopharmaceuticals, the industry must still come together to educate the public on the basics of cannabis and derived products like CBD to continue this momentum. While regulations will eventually catch up and guidance will appear, the impetus is on physicians, manufacturers, and consumers to create clarity in the status quo.
References
[1] MacCallum CA & Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-19.
[2] Williams A, et al. “Update on the EU Regulation of CBD in Foods and Vaping.” Available at: https://www. biosliceblog.com/2019/07/update-on-the-eu-regulation-ofcbd-in-foods-and-cosmetics/ Accessed: February 25, 2020.
[3] Williams S, et al. “CBD Is Not Safe, Says Former FDA Chief Scott Gottlieb.” Available at: https://www.fool. com/investing/2019/11/17/cbd-is-not-safe-says-formerfda-chief-scott-gottli.aspx Accessed: February 25, 2020.
[4] Ewing LE, et al. Hepatotoxicity of a cannabidiolrich cannabis extract in the mouse model. Molecules. 2019;24(9):1-17.
