Should the industrial hemp industry fold to federal pressure regarding cannabidiol?

A concerted effort by the federal government is putting significant pressure on the cannbidiol market. Will it work?

Cannabidiol (CBD) is the non-psychoactive cannabinoid cousin of delta-9-tetrahydrocannibinol (THC, the molecule mainly responsible for the cannabis-associated "high") and the market for it has simply exploded since the reinvigoration of the global industrial hemp market.

 The molecular structure of cannabidiol (CBD).

The molecular structure of cannabidiol (CBD).

What do we know about CBD?

CBD is not THC, as this infographic will show you.  In short, the retail cannabis marketplace thrives on short squat female plants that produce 20-30% THC in the resultant flowers while the industrial hemp marketplace thrives on (mostly) tall lean males that contain minute quantities of THC and can be harvested for long, strong fibers (for example).  Most regulatory agencies around the world consider anything with less than 1% THC industrial hemp (non-drug-type Cannabis sativa); however, most technically define hemp as 0.3% THC or less and, practically, the levels of THC found in hemp strains grown today are much less than this.  The amounts of CBD can vary in both drug-type Cannabis sativa (grown for medical and retail markets) and non-drug-type industrial hemp.  Often, retail cannabis has negligible levels of CBD, followed by medical-grade cannabis and hemp - both of which have strains that where CBD can reach into the 20-25% range.  

 Charlotte's Web is a well-known low-THC, high-CBD strain of  Cannabis sativa .

Charlotte's Web is a well-known low-THC, high-CBD strain of Cannabis sativa.

CBD does not possess psychoactive properties; however, it is *the* driving factor right now for the medical uses of cannabis.  Its use to treat special forms of childhood epilepsy that are resistant to conventional treatment has been nothing short of spectacular.  This is evidenced by the fact that forty (40) states now allow patients access to CBD, as opposed to just 23 and the District of Columbia who allow patients access to THC via drug-type Cannabis sativa.

CBD has been demonstrated to provide a spectrum a health benefits due to its ability to act as a strong antagonist (i.e. blocker) of the endocannabinoidome (ECD) receptors.  The ECD is the extended view of how the research community now views the endogenous cannabinoid signaling system found in man (the "endocannabinoid system," similar to the enkephalin system and its series of opioid receptors through which the effects of endorphins, morphine, heroin and synthetic opioids (like Percocet, Oxycontin, etc.) etc are felt. 

An exhaustive view of CBD pharmacology and its effects are beyond the scope of this article, but the reader is referred to Welty, T. E., Luebke, A., & Gidal, B. E. (2014). Cannabidiol : Promise and Pitfalls. Epilepsy Currents, 14(5), 250–252.  Some discoveries that have been made recently include:

  • Over 65 discrete targets have been reported in the literature for CBD, however, treatment of neurological disease associated the regulation of intracellular calcium levels shows promise. Ibeas Bih, C., Chen, T., Nunn, A. V. W., Bazelot, M., Dallas, M., & Whalley, B. J. (2015). Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics, (AUGUST).

  • Zhornitsky and Potvein (2012) reviewed 18 randomized clinical trials in human populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study). Zhornitsky, S., & Potvin, S. (2012). Cannabidiol in humans-The quest for therapeutic targets. Pharmaceuticals, 5(5), 529–552.

  • CBD may have utility in treating human diseases and disorders known to involve activation of the immune system and associated oxidative stress, such as rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemiareperfusion injury, depression, and neuropathic painBooz, G. W. (2011). Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radical Biology Medicine, 51(5), 1054–1061. 
  • Preclinical (animal) data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature. Stanley, C. P., Hind, W. H., & O’Sullivan, S. E. (2013). Is the cardiovascular system a therapeutic target for cannabidiol? British Journal of Clinical Pharmacology, 75(2), 313–322. 
  • CBD might reduce seizure frequency and might have an adequate
    safety profile in children and young adults with highly treatment-resistant epilepsyDevinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., … Cilio, M. R. (2015). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet Neurology, (January 2016). 

GW Pharmaceuticals is perhaps the biggest player in the CBD drug development market and not only commercialized the world’s first cannabis extract prescription drug (a mix of THC and CBD, Sativex, for the treatment of spasticity due to MS), but has also "Orphan Drug Designation" from the FDA for Epidolex, a pure CBD drug, for the treatment of Dravet and Lennox-Gastaut syndromes, severe, drug-resistant epilepsy syndromes. GW’s product pipeline also includes compounds in Phase 1 and 2 clinical development for glioma, ulcerative colitis, type‑2 diabetes, and schizophrenia.

CBD products and the CBD "gold rush" is big business and the federal and state governments knows it.  The fledgling industrial hemp market is looking to produce CBD on a large-scale from non-drug-type hemp plants that are legal in those states that have regulated markets (about 2 dozen, including West Virginia, Kentucky and Colorado). 

Hasn't this come up before?

Absolutely - like here for example. In HIA v DEA (2003), the DEA tried to write rules and related retroactive interpretations of the Controlled Substance Act impacting certain cannabinoids that were expressly covered under the original intent of the law.  While the court case told the DEA it could not go back and change the intent of the law, it still maintains the position that CBD is a Schedule 1 substance with no medical benefit, just like marijuana.

The confusion will remain as CBD is not specifically covered or defined under the CSA.

What is the government doing?

It appears that both the state and federal governments have initiated a concerted effort to quell the raidly expanding CBD market.  Reasons are not clear but evidence is abundant.  In addition to the continued pressure that DEA's questionable policy on CBD's legality brings to bear, both the Food & Drug Administration (FDA) and Customs & Border Patrol (CBP) have stepped up enforcement efforts.   

FDA: Despite on-going discussion between law firm Hoban & Feola LLC and the FDA regarding nationwide retail placement of CBD products, FDA posted new information on its website regarding medical cannabis in May 2015.  In this non-binding, informal "Q&A" document posted online, FDA declared CBD products are excluded from the definition of "dietary supplement" as found in the Federal Food, Drug and Cosmetic Act (FFDCA).  As a follow up to this industry notice, FDA issued warning letters to several companies marketing dietary supplement CBD products in February 2016.  First and foremost, FDA took issue with the unsupported health claims made on the packaging of these products.  Next, FDA claimed "CBD Oil" is not allowable as an ingredient due to previous investigation as a drug. In other words, another company submitted an official application to FDA for use of CBD Oil as a drug.  

CBP: Starting in August 2015, there was an uptick in imprted hemp good seizures at the border.  According to Hoban & Feola, these were not announced, records were not kept and collective finger-pointing was left these early seizures "unresolved."  CBP claimed these were illegal dietary supplement imports and referred to FDA for action, but none was taken and the shipments were released. Later that year, CBP started testing for THC concentration and using its federal authority instead.  By November, CPB issued a "zero tolerance" policy statement, citing the DEA policy that HIA had the court invalidate in 2003.  During 2015, CBP went from a position of allowing up to 0.3 THC into the country to allowing NO, NONE, ZERO, ZILCH in a CBD product.

Why the hemp industry should press ahead...

While the current situation and pressure coming from the federal government is serious, it is also stands on shaky ground.  The DEA's position on CBD is tenous and could be rendered moot with a simple legislative fix, the FDA hasn't issued any binding guidance on this and its interpretation could be (and has been) challenged, and the CPB logic is, quite simply, bizarre if not poorly justified.

The simple legislative fix I refer to stands before Congress now and has enjoyed mulitple trips to Congress since 2009 - currently known as the Industrial Hemp Farming Act of 2015.  It would simply amend the CSA to exclude industrial hemp from the definition of "marijuana." It would define hemp as no more than 0.3 % THC. It would free the industrial hemp market from the shackles it has been in since the 1930s and allow many folks to participate in a new and growing agricultural market.

FDA's guidance to date consists of an online "Q&A" and some warning letters.  These would not be considered actions binding on the regulated community. The letters invite the regulated community to submit data proving the validity of existing market claims and some companies, like CV Sciences (formerly CannaVest), have done so and pointed out the confusion that remains with the FDA decision.  It should also be pointed out that other dietary supplements still on the market today have received a equal magnitude of scrutiny from FDA. Finally, Hoban & Feola point out that in no way has FDA made a determination that CBD products are illegal or non-compliant with CSA -- as both DEA and CPB have.

I believe this attack on the industrial hemp market will pass; however, for now, one is very wise to consult heavily with lawyers and consultants moving into 2016.