Hazy Forecast: GW Pharma Seeks FDA Approval, Complicates CBD Landscape

The closer cannabis gets to being recognized medicine, the cloudier its future seems to be.

GW Pharmaceuticals, an England-based biotech company, has spent nearly 20 years working to bring a botanical cannabis-based medication to market. Although GW was successful in launching Sativex a 1:1 THC:Cannabidiol formulation in much of the world, the United States has proven more difficult to enter. Currently only synthetic tetrahydrocannabinol (THC), under the brand names Marinol and recently Syndros, has been approved by the Food and Drug Administration (FDA).

Dr. Ethan Russo, former president of the International Cannabinoid Research Society and senior medical advisor for GW, said a botanical should prove superior to synthetic cannabinoids.

“Philosophically, I believe that cannabidiol should derive from the plant that makes it naturally,” Russo said. “Epidiolex is not purely CBD [cannabidiol], but rather is an extract that contains some terpenoid components. Cannabis achieves many of its medicinal properties from herbal synergy—a boosting of beneficial effects from its many components.”

The roadblock on FDA approval for natural cannabis products may soon change because, on October 30, GW finished its submission of a New Drug Application (NDA) to the FDA for Epidiolex (cannabidiol) to help manage seizures associated with two rare epilepsy-related diseases: Lennox-Gastaut syndrome (LGS) and Dravet syndrome.

According to Russo, this was a big step forward for medical cannabis.

“I am pleased to see that Epidiolex has completed its NDA submission to the FDA, and am proud that I was able to assist in early stages of its clinical development program,” Russo said. “It is clear to me that certain consumers and many physicians will only accept a pharmaceutical form of cannabis-based medicine and, certainly, Epidiolex has proven to be a safe and effective option for the most severely affected epilepsy patients with Dravet and Lennox-Gastaut syndromes in the clinical trials. I believe that its approval, when it happens, will also lead to a more serious examination in the USA of the medicinal properties of other cannabis-based formulations.”

Russo was on the right track with his comments about Epidiolex triggering examinations related to medical cannabis in the US. Unfortunately for many in the US hemp industry, the examinations appear to be catching them off guard.

The FDA sent warning letters to four of the largest hemp CBD companies in the country, the day after GW filed the NDA for Epidiolex, which is a CBD extract. The letters cite unsubstantiated claims related to more than 25 different products spanning multiple product web pages, online stores, and social media web sites. The FDA says the companies used these online platforms to make unfounded claims about their products.

“The companies received these warning letters, in part, because of the egregiousness of the claims made about their products and the determination that inaction posed a potential risk to public health,” FDA spokesman Michael Felberbaum said via email. “In this case, the companies distributed products with unsubstantiated claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anti-cancer claims …The FDA will continue to monitor and take swift action against companies that egregiously promote and sell unproven treatments. When a product is in violation of the Federal Food, Drug & Cosmetic Act, the FDA considers many factors in deciding whether or not to issue warning letters. Those factors include, among other things, agency resources and the threat to the public health.”

These claims are at issue because all food and drugs fall under the scope of the Food, Drug and Cosmetic Act along with the FDA. Because the products aren’t FDA-approved drugs, they are being sold as food or nutritional supplements. However, under the law, supplements may not be sold with claims that they can be used to treat or cure diseases. Beyond the issue with claims, the FDA further questions the ability of these manufacturers to call the products supplements.

The Dietary Health and Safety Act requires that all ingredients for food or supplements not in use before 1994 file a New Dietary Ingredient Application to market a product in the US. While hemp seed—with its trace cannabinoids—which is exempted in the CSA, may legally be used in food and supplement products because they have been in use since prior to 1994, CBD extracts weren’t in common use prior to 1994 and so require the NDI filing. One NDI for cannabinoids from hemp was submitted by Jeffrey Nathan Schirripa in 2015 on behalf of “Purevolution Enterprise” for a new supplement called “Neuroprotecting Antioxidants.” However, the application was turned down in a December 15, 2015, response to the notification. The FDA told Schirripa that if a product contains CBD, it will not qualify as a dietary supplement.

“This is because CBD has been authorized for investigations as a new drug for which substantial clinical investigations have been instituted, and for which the existence of such investigations has been made public,” Robert J. Durkin, former acting director of FDA’s Division of Dietary Supplement Programs, wrote in the letter. “Prior to such authorization it was not marketed as a dietary supplement or as a food.”

The aforementioned Dietary Health and Safety Act also includes a rule that says that once an ingredient is in a drug product that has been approved or authorized for investigation as a new drug for which substantial clinical investigations have been instituted, it cannot be sold or used as a food or supplement, unless it was used as a supplement prior to the drug investigation. GW started new drug investigational trials for CBD-containing drugs Sativex and Epidiolex in 2007 and 2014 respectively. Both trials preceded the filing for a new dietary ingredient for CBD supplements in 2015. This effectively permanently blocked the creation of a hemp CBD-extract food supplement even following rescheduling.

Dr. Russo attempted to explain the legal and treatment efficacy problems related to using hemp as a source for CBD under current laws.

“As I have stated publicly on many occasions, hemp refuse is a poor source for medicine,” Russo said. “Cannabinoids, including CBD, are present in this material in concentrations that are a tiny fraction of those in the unfertilized female flowers of dedicated cannabis chemovars selectively bred for high CBD production. In order to extract CBD from hemp refuse, it needs to be greatly concentrated, which also will concentrate pesticides and other extraneous and possibly toxic contaminants. Additionally, there is a prevalent misconception that making products this way renders them legal throughout the USA. This is simple erroneous. The Controlled Substances Act of 1970 indicates that hemp stalks are not controlled, but once someone extracts them chemically, the material is again illegal. CBD remains a Schedule I forbidden substance in this country and will remain so until or unless it is rescheduled by Congress. Even when Epidiolex becomes FDA-approved, that does not mean that other non-pharmaceutical CBD products will be legal.”

From the CSA:

“The term ‘marihuana’ means all parts of the plant Cannabis sativa L., whether growing or not;  the seeds thereof;  the resin extracted from any part of such plant;  and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin. Such term does not include the mature stalks of such plant, fiber produced from such stalks, oil or cake made from the seeds of such plant, any other compound, manufacture, salt, derivative, mixture, or preparation of such mature stalks (except the resin extracted therefrom), fiber, oil, or cake, or the sterilized seed of such plant which is incapable of germination.”

A DEA spokesperson affirmed Russo’s words and further explained that many people erroneously believe the 2014 Farm Bill authorized much of the activity with CBD.

One of the bones of contention between the hemp industry and the DEA lies in the wording of the Farm Bill. Under definitions, it claims: “the term ‘‘industrial hemp’’ means the plant Cannabis sativa L. and any part of such plant, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.” This wording seems to set a different definition for industrial hemp. The DEA spokesman said that definition and the protections from the CSA for cultivation in the Farm Bill only pertain to plants grown as part of research projects with the agriculture department and universities.

The spokesman said the Farm Bill only allows research and cultivation and that any activity beyond cultivation or research must follow the CSA and Dietary Safety Act and other laws that set the rules for supplements, as well as defining which parts of the cannabis plant can be sold for human consumption. The spokesman said that the DEA was only interested in hemp products intended for human consumption and that hemp fiber and related creations weren’t under their review. He added that while the FDA and DEA are attempting to reign in the hemp CBD industry they wouldn’t be targeting the end users of the products.

“I can assure you that the DEA is excited about the possibility of approved, regulated cannabis drugs replacing what we have currently across the states,” a DEA spokesman said.

Joel Stanley, CEO of CW Hemp—one of the producers that received an FDA warning letter—recently argued in an opinion letter that Congress intended to protect and define industrial hemp as shown in the Consolidated Appropriations Act, 2017. The Act says: “[N]one of the funds made available in this Act or any other Act may be used to prohibit the transportation, processing, sale, or use of industrial hemp that is grown or cultivated in accordance with section 7606 of the Agricultural Act of 2014, within or outside the State in which the industrial hemp is grown or cultivated.”

Arguments surrounding these issues and definitions are playing out in the Ninth Circuit Court of Appeals in the case of the Hemp Industries Association vs. the DEA. The Hemp Industry is claiming the Farm Bill and other legislation frames industrial hemp only in terms of THC content and should allow CBD extracts in contrast to the previously mentioned legal definitions the DEA and FDA claim to be following. The case is occurring as the FDA reviews the NDA for Epidiolex, and prepares to potentially approve the first-ever cannabis derived product available for prescription in the US.

For many, the fight between hemp CBD vs. GW is about corporations vs. small businesses, but it’s important not to miss that Insys Therapeutics, which also makes opiates, recently won a Schedule II designation for the synthetic liquid THC product Syndros. The company also has a synthetic CBD formulation in FDA trials. Will the answer lie in hemp-sourced CBD, synthetic CBD, or pharmaceutically formulated botanical CBD or a combination of all three? Only time will tell.