Trends in Medical Cannabis: Epidiolex and the FDA

In April 2018 a US Food and Drug Administration (FDA) advisory committee recommended the approval of Epidiolex: a cannabis plant-derived, prescription use epilepsy drug. The FDA has not yet approved the drug, and many believe they will not at this stage. But, this recommendation has raised hope across the medical cannabis research community as approval would represent the first formal FDA acknowledgment of the medical uses of the cannabis plant. The move has also stoked an ongoing and sometimes contentious debate: what’s best, synthetic or plant-derived cannabinoids?

To shed some light on what this development means and the pros and cons of synthetic and natural cannabinoids we spoke to Dr. George E. Anastassov, MD, DDS, MBA, CEO of AXIM Biotechnologies.

JR: Everyone has an opinion on how the cannabis plant should be utilized for medicinal purposes. What are the benefits of botanically-derived cannabinoids over synthetic ones and vice versa? 

GA: It depends whether one believes in Professor Mechoulam’s theory of the “Entourage Effect.” What that theory proposes is that cannabinoids have a holistic effect meaning the sum of their medicinal effects is much greater compared to that of isolated cannabinoids. To date, more than 100 cannabinoids have been including the well-known classes such as THC, CBD, CBG and CBN.  Besides these, the cannabis plant contains more than 700 other molecules including things like terpenes, antioxidants, and vitamins. Despite all of this, it has not yet been established whether naturally extracted and purified cannabinoids are more effective as medicines than synthetic or vice versa. What we do know is that it is extremely difficult to produce pharmaceutical grade, purified (99.8% plus purity) cannabinoids from botanical material. However, AXIM has accomplished just that. We are now able to create extremely high purity cannabinoids but, so far this has only been possible with THC and CBD. Unfortunately, for now, the process to produce them is rather complicated and extremely expensive. At the consumer level, cannabinoids that have been naturally extracted and purified from botanical material, often referred to as “organic,” have more appeal than their synthetic counterparts. It is worth mentioning that the process to create this kind of product to pharmaceutical standards must start with a Current Good Manufacturing Practice (cGMP) compliant cannabis plant. Only one company in the world has this designation, Bedrocan in The Netherlands and, every subsequent step must be cGMP as well.

JR: Can you comment on the recent move by an FDA advisory committee to recommend the approval of Epidiolex? 

GA: We will wait until June 27th and see what the final recommendation will be. There may be issues with the quality requirements stipulated by the FDA. It is a question of cGMP. The FDA has extremely strict criteria for purity the of pharmaceuticals. There should be no more than 0.2% impurities. That means that the CBD in Epidiolex should be 99.8% pure. This is not the case. For the sake of GW Pharmaceuticals, I hope that all goes smoothly. 

JR: What does this mean for other biotech companies engaged in cannabinoid-focused research? And, what other trends are you keeping an eye on?

GA: If Epidiolex is approved by the FDA (keep in mind that Sativex has been on the FDA’s desk for a decade and is not approved) it will signal a shift in the FDA stance on naturally extracted cannabinoids, which are currently scheduled by the Drug Enforcement Agency (DEA) as Schedule I. If approved, the big question is how it will be scheduled? Schedule II or III? This makes a major difference for GW Pharmaceuticals. To start with, it will have to be produced in the United States where there is no reliable supplier of pharma grade cannabis. This will mean that they will either have to reformulate it with synthetic cannabidiol (CBD) and carry out the necessary studies to support reformulation or petition the DEA to grow their own cannabis in the USA. If their active pharmaceutical ingredient, CBD meets the purity criteria, which is not the case with Sativex, it will have a better chance at gaining registration. It will also be the first natural cannabinoid-based drug approved by the FDA. 

JR: How does the work done at AXIM Biotechnologies tie in to all of this? What are you developing and what does it enable? 

GA: AXIM is the only company which has the technology, access to cGMP cannabis plants, and produces pharma grade, pure, botanical THC and CBD at 99.9% purity. We also work with synthetic cannabinoids and closely follow the trends at the FDA. We are prepared to proceed with whatever is deemed “politically correct” by FDA standards. We have formulated a number of products and are placing them strategically in AXIM’s pipeline of prescription, over-the-counter, and consumer products, such as CanChew Plus® Chewing Gum to treat Inflammatory Bowel Disease (IBS), MedChew-1401 Chewing Gum to treat Multiple Sclerosis Pain and Spasticity, and our dronabinol therapeutic equivalence program. 

We recently announced a long-term purchase agreement with Noramco for dronabinol to be used in AXIM’s clinical trials for the treatment of chemotherapy-induced nausea andvomiting (CINV) and anorexia associated with weight loss in patients with cancer or AIDS. AXIM will microencapsulate the active pharmaceutical ingredient (API) and formulate it into its proprietary controlled-release chewing gum delivery system, which will go through a clinical study comparing the bioavailability and therapeutic equivalence of the Company’s product to the FDA-approved reference listed drug (RLD) Marinol®.

Dr. George E. Anastassov was speaking to Jack Rudd, Managing Editor, Analytical Cannabis.