Phytocannabinoids: Hemp vs. MarijuanaWhile both hemp and marijuana are Cannabis sativa L, the crucial difference between the two is the level of Tetrahydrocannabinol (THC), the cannabinoid that creates the psychoactive properties associated with the ingestion of marijuana. By definition, hemp contains less than 0.03% THC by dry weight, unable to cause intoxication, but still rich in other cannabinoids such as cannabinoidiol (CBD) and plant compounds such as terpenes and flavenoids. In fact, explains Jane Wilson, director of program development at American Herbal Products Assocation (AHPA), “Cannabis plants used as marijuana for medical or adult use purposes generally have THC as the most abundant cannabinoid, whereas hemp plants are more likely to have CBD as the most abundant and THC must be < 0.3%.”
Now, dispensaries in states that have legalized medical and/or recreational marijuana also market the CBD content in their tinctures, understanding the value or the cannabinoid for human health. That makes for an interesting dynamic between those who advocate for marijuana and those who advocate for hemp. “The federal prohibition on marijuana continues to limit the expansion of the hemp industry as well,” says Wilson. “While companies can legally import industrial hemp materials for the production of products such as CBD extracts, hemp industry efforts to gain greater acceptance for the domestic cultivation of hemp as a commodity crop have not yet been entirely successful.”
While they are linked in some ways, business interests may conflict, as Jared Berry, CEO of Carlsbad, CA-based Isodiol explains. “The last thing marijuana growers and providers who operate under state laws want to see is imported hemp products come in to their marketplace and compete at lower prices taking a large chunk of their profits,” he says. “This is why there have been ridiculous claims that marijuana CBD is medically superior to hemp CBD as if somehow the molecule can change to cause this elevated result.”
While marijuana is a hot button issue in the mainstream, Colleen Keahey, executive director of the Hemp Industries Association (HIA), points out that the hemp industry has made more progress and has a real advantage over marijuana. “I think industrial hemp provides an opportunity for more legitimized and standardized business practices as they relate to the development of products that are derived from cannabis. Industrial hemp definitely has more of a legal framework in order to move forward because of the nature of its distinction from marijuana,” she explains. “So I think that if anything, as industrial hemp companies, we’re getting into the space a little earlier with regards to evaluating how do we create commercial environments for industrial hemp manufacturing that follow good manufacturing practices.”
Berry concurs. “Hemp is established volumes deep in case law and throughout nations as an industrial product for textiles, food and many other commodities,” he states. “High THC plants can be extremely psychoactive and although they may offer tremendous medical value, there will always be heavier and stricter regulations on any mind-altering substance.”
Legal StatusDrug Enforcement Authority. As you well know, the Drug Enforcement Authority (DEA) places marijuana under Schedule 1, making it an illegal narcotic. Most recently, on December 14, 2016, DEA issued a final rule that created a new Administration Controlled Substances Code Number for marijuana extracts, defined as “an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis, other than the separated resin (whether crude or purified) obtained from the plant” (1). Now, DEA has always considered marijuana extracts to be under Schedule 1 but this document makes it official. However, what has created a great deal of confusion in the natural products industry is that DEA does not appear to differentiate the types of genus cannabis that separates marijuana and hemp when it states “any plant of the genus Cannabis.”
Keahey confirms this confusion, but assures that DEA is overstepping its authority. “HIA’s position is that industrial hemp is defined distinctly from marijuana and the DEA administrative rule regarding cannabinoids does not offer any language that honors that distinction,” she explains. “Instead, that ruling suggests all genus cannabis without citing an exemption for industrial hemp. That has been alarming to the industry but overall we believe that the DEA really cannot regulate cannabinoids that are derived from an industrial hemp plant variety as it is defined distinct from marijuana that is in the American Agricultural Act of 2014 in Section 7606, the Legitimacy of Industrial Hemp Research Act.”
In fact, many manufacturers interviewed for this article expressed no concern for the legal status of their products in the marketplace, but frustration about how DEA has only sown unwarranted fear and trepidation about phytocannabinoids. “Our lawyers don’t see any issues, we haven’t seen any negative impact on our business, our business continues to grow. We have seen the DEA’s commentary result in a lot of fear though. We had a lot of questions from our customers, we’ve had business partners that get nervous and back away from deals, we’ve had advertising partners back away from deals. It definitely has had a ripple through the industry as the DEA intended it to do,” says Ashley Grace, CMO of CW Hemp, Denver, CO.
Bill Arnold, CEO, Cannoid, LLC based in Aurora, CO describes the rule change as simple housekeeping by DEA, directed not at the natural products industry but the pharmaceutical industry. To put it into perspective, he explains that companies pursuing pharmaceutical development of cannabinoids require isolates such as molecularly pure CBD in order to properly control and study the compounds. GW Pharmaceuticals for example is seeking drug approval from the U.S. Food and Drug Administration (FDA) for its product Epidiolex that is synthesized from CBD isolates. Once this gets final approval as a drug, these isolates will become controlled substances, similar to opioids or THC. “These companies essentially made CBD a drug, but they didn’t have the proper rules within the DEA’s Controlled Substances Act to manage those products,” says Arnold. DEA essentially needed a way to track the sale and import of CBD isolates the way it would opioids which requires special permits and strict controls on how it’s kept and studied.
However, he does concede that the nomenclature used by DEA was extremely clumsy, using terms like “extracts” instead of industry terminology like “isolates” which would have created a narrower, more specific definition as well as neglecting to use language that differentiates hemp and marijuana. But, as mentioned by other experts, this difference is memorialized in other legislation such as the Farm Bill.It is important that the trade stop focusing on a single magic bullet molecule CBD and start focusing on the more important class of compounds called phytocannabinoids.
— Carl Germano, CNS, CDN, Consulting International, Ltd.
That being said, the new drug code does indeed effect CBD isolates and will harm companies that spike their oils with isolates rather than using whole hemp extracts with naturally- occurring cannabinoids. This may be positive for phytocannabinoids companies within the natural products industry because it will eliminate unscrupulous manufacturers and create a much more fair marketplace for full spectrum phytocannabinoid products.
While the Farm Bill does make a distinction between marijuana and hemp, what complicates matters is the different interpretations of the law by regulatory agencies and those manufacturing the products. Wilson explains that “the industrial hemp amendment to the 2014 Farm Bill does allow states to conduct industrial hemp research and pilot projects, but DEA has not interpreted the amendment to allow for commercial production of hemp products such as CBD.”
On the other hand, “DEA policy does not affect companies that sell European industrial hemp stalk oil products (that contain naturally occurring phytocannabinoids), classified and legally imported into the U.S. as a conventional food and dietary ingredient,” explains Carl Germano, CNS, CDN, Consulting International Ltd. “As such, hemp stalk oil raw materials that comply with USDA, FDA and DEA regulations receive customs clearance and are legal US imports.”
CW Hemp, which grows and harvests its own hemp in Colorado, however, defends its legality as guaranteed under the Farm Bill and later clarified in the 2015 Consolidated Appropriated Omnibus Act. The company’s legal statement explains that “CW Botanicals is a duly registered hemp producer in the state of Colorado, which permits and regulates Farm Bill-authorized agricultural pilot programs in that state. The Colorado Department of Agriculture...has provided written guidance that expressly authorizes CW Botanicals (and its affiliated companies) to ‘process, sell or distribute hemp...and...also sell hemp products made from hemp.”
The firm’s opinion is that this is in line with the language of the Farm Bill which under Section 7606 states, “Nothwithstanding the Controlled Substances Act...or any other Federal Law, an institution of higher education...or a State department of agriculture may grow or cultivate industrial hemp.” Following DEA’s efforts to prevent the important of hemp seeds the Kentucky Department of Agriculture and the impending lawsuit, clarification was provided in the 2015 Consolidated Appropriated Omnibus Act which stated, “None of the funds made available in this Act or any other Act may be used...to prohibit the transportation, sale or use of industrial hemp that is grown or cultivated in accordance with subsecton 7606 of the Agricultural Act of 2014, within or outside the State in which the industrial hemp is grown or cultivated.”
Grace contends that with its U.S.-grown hemp, CW Hemp is able to distinguish itself from those products made from imported hemp. While brands may import oil extracted from hemp grown in Europe and even China, Grace says this can pose a problem. “Oftentimes that hemp is grown more for industrial purposes and you could turn industrial hemp into phytocannabinoid-rich oil, the challenge there is that it takes a lot of plant material to do that and your putting a lot more chance for pesticides and contamination from the environment into those products and the next time you buy those products, it likely has a different source of plant material,” he explains.
CW Hemp on the other hand, grows a single strain of hemp that Grace says is rich in CBD because its short, stout stature allows for more flowers to grow, enabling high CBD content in the seeds and stock used to make their oils. “Every bottle, every drop is always the same with Charlotte’s Web,” Grace explains. “We clone those plants, we grow them by hand, plant them by hand, we oversee it — the Stanley Brothers family — so we’re completely vertically integrated, produce all the hemp ourselves then bring it to an FDA-registered facility in Boulder, CO and process it under third-party audited good manufacturing practices.”
This seed-to-shelf manufacturing quality and consistency is something many retailers and consumers are looking for in their products, but there is also a great deal of quality control present in phytocannabinoid products that employ imported hemp oil, even if it comes from multiple source. In fact, says Arnold, there can be certain advantages to this. Cannoid, which manufacturers Entourage Hemp takes a unique approach to sourcing and developing its phytocannabinoid products. While most manufacturers seek a consistent quality source for their hemp oil, Arnold says “Companies that want stability and potency in product type are going to be limited to that product as being their primary source of cannabinoids...in terms of cannabinoid profile the starting material provides.”
Cannoid takes what Arnold calls an artisanal approach. “We’ll reach out directly to family farms in Europe that might have a certain strain of hemp that produces high levels of a certain cannabinoid. The idea is to build up a full profile, CBC and CBD are the most prominent cannabinoids in our products but our perspective is to try to blend all of these source oils so that we can maximize and have the fullest spectrum in the industry,” he explains. They are able to maintain quality by having stringent guidelines in place for suppliers to meet basic qualifications. “The idea is that you establish a baseline for quality that all your suppliers are required to meet and then you have ongoing validation throughout the relationship,” says Arnold.
If something should go wrong with the supply of oil such as pesticide contamination from neighboring farm, they have the flexibility in their supply chain to move away from that supplier, Arnold explains. Cannoid is also able to control the potency of final product in their lab and ensure consistency across their inventory. “We don’t rely on the analytical testing of the source material to determine what our final potencies are or determine what that final product will be,” says Arnold. “I’ll put in sometimes a dozen different oils and I can, based on analytical testing, increase or decrease the amount of each of those oils to arrive at a specific point.”
Stuart Titus, Ph.D. and CEO of HempMeds based in Poway, CA, for his part, boasts about a study published in the Journal of Regulatory Science. In the study, 23 phytocannabinoid products were purchased on the internet and tested to determine the accuracy of their label claims. Only eight products were explicitly consistent with their label claims, of which, three were HempMeds products. Their products are also made with imported oil. This demonstrates that finding the right manufacturer is crucial in giving your customers, safe, consistent and quality products.
U.S. Food and Drug Administration. Another point of confusion with phytocannabinoids is whether they can be marketed as dietary supplements. The point of contention in this instance is CBD. Wilson explains that FDA in May of 2015 made public its view that they do not consider CBD a dietary supplement because it is being evaluated as an Investigational New Drug (IND) and they have no evidence that CBD existed in the food supply prior to these clinical investigations. Additionally, she says, “There is also the question of whether a New Dietary Ingredient submittal would be necessary to establish CBD or other phytocannabinoids as lawful dietary ingredients to be used in supplements unless it can be shown they were in the food supply prior to the adoption of DSHEA in 1994.”
Brands like CV Sciences dispute this position, stating, “Notwithstanding the FDA’s Q&A Posting, it is our opinion, which is broadly shared by the marketplace, that CBD has been marketed as a dietary supplement prior to commencement and public notice of any substantial clinical investigations instituted on CBD, as the investigations that were publicized were not substantial, due to being limited in number and preliminary in nature, thereby rendering the IND preclusion inapplicable.”The Endocannabinoid System governs functions such as mood, sleep, appetite, hormone production, digestion of food, metabolism, basically every function of the human body. — Stuart Titus, Ph.D., HempMeds
For this reason, there is a disparity in the way phytocannabinoid products are marketed that can be confusing. You will see quality products that market themselves as hemp oil with a full spectrum of phytocannabinoids but some may or may not include the CBD content of their product on their label. The companies that do not include CBD content on their label do so out of an abundance of caution. Grace expresses frustration in the inconsistency across the marketplace, “It’s challenging because number one it’s not what our product is, but on the negative side it’s confusing because there are a lot of people out there marketing CBD.” Charlotte’s Web wants to avoid the association of CBD not just because of FDA’s opinion but because the focus on CBD draws attention from the importance of hemp’s many other cannabinoids and plant compounds. Germano concurs. “It is important that the trade stop focusing on a single magic bullet molecule CBD and start focusing on the more important class of compounds called phytocannabinoids,” he states.
However, because CBD is more recognizable, other brands opt to display its content on product labels. “We decided to call our brand ‘PlusCBD Oil’ because we recognized that consumers had done their research about the potential benefits of CBD,” explains Sarah Syed, director of marketing, CV Sciences, Las Vegas, NV. “We wanted to make it as easy as possible for them to walk into their local health food store to find just that. Our products contain the phytocannabinoid matrix that exists in all hemp products.”
Ultimately, what these brands do similarly is that they do not make any health claims about their products that would put them at risk of drawing the ire of FDA. Industry has to continue conducting research to validate anecdotal and emerging data about phytocannabinoids’ importance to human health. In the meantime, it is up to consumers to educate themselves and you, the retailer to help customers understand why phytocannabinoids are beneficial.
The Whole PackageCBD has received a great deal of attention as it is the second more prominent cannabinoid in marijuana and the most prominent cannabinoid in hemp. However, although it may be the most prominent, its beneficial properties are not achieved in isolation from other cannabinoids and plant compounds. “There are about 500 other chemical compounds within the plant,” says Titus. “We have between 80 and 100 different trace cannabinoids in our crop about another 400 plant compounds such as terpenoids and flavenoids.”
“Each [cannabinoid] is very unique from each other but in the same ‘family,’” explains Berry. “It is believed that when combined together there is a more powerful ‘synergistic effect’ when ingested. This theory was born in Jerusalem in 1999. It was labeled as the ‘entourage’ effect and is only produced with ‘full spectrum’ oil.”
Germano also expresses the importance of this synergistic relationship between all phytocannabinoids in hemp citing a review published in The British Journal of Pharmacology where the author breaks down the many phytocannabinoids found in hemp. Research has shown that CBD has a long list of therapeutic properties, including potential anti-anxiety and antidepressant activity, being an analgesic, a neuroprotective antioxidant “more potent than ascorbate and tocopherol,” an anticonvulsant and even shown to be cytotoxic in breast cancer cell, to name a few (2). However, hemp’s other cannabinoids have their own abilities which when put together enhance the effects of its dominant constituent. For example, CBG has analgesic and anti-erythemic effects “said to surpass those of THC,” and says the author, “is the next most effective phytocannabinoid against breast cancer after CBD” (2).
The paper also explores the importance of terpenoids of which there are 200 in cannabis (2). Terpenoids’ prominence in the plant is demonstrated by the fact that terpenoids are responsible for cannabis’ distinct aroma. D-limonene, for example, is the most widely distributed terpenoid in nature and the precursor to other monoterpenoids. Common in citrus essential oils, various studies have found that citrus oils rich in limonene eased symptoms of anxiety and depression in subjects and limonene has also been shown to produce apoptosis of breast cancer cells (2). Another terpenoid, caryophyllene, is frequently the predominant terpenoid overall in cannabis extracts. Research has found that it has anti-inflammatory properties and has been tested as a gastric cytoprotective for the treatment of stomach ulcers some time ago. Significantly, caryophyllene has been demonstrated to be “a selective full agonist at [receptor] CB2, the first proven phytocannabinoid beyond the cannabis genus” (2).
“Retailers should avoid looking for isolated, purified, crystallized CBD as it is not as effective as compared to an entourage of phytocannabinoids,” says Germano. As mentioned previously, isolates are also considered drugs by FDA and DEA, making it illegal to market in dietary supplements. However, as less scrupulous manufacturers are beginning to see the value of being full spectrum, Berry warns that retailers should look out for brands that claim to be full spectrum but are not. “Due to the extraction methods used to increase the levels of CBD, the other cannabinoids are removed,” he explains. “This isn't ‘full spectrum.’”
The Endocannabinoid SystemPhytocannabinoids such as terpenoids exist outside of cannabis and, says Titus, cannabinoids such as CBD are also abundant in other sources plant sources, particularly flax. In fact, phytocannabinoids play a crucial role in our health by supporting the endocannabinoid system. “This system governs functions such as mood, sleep, appetite, hormone production, digestion of food, metabolism, basically every function of the human body,” explains Titus. “So we really believe these plant-based cannabinoids can supplement this very large self regulatory system and bring us to a much higher level of overall health and wellness.” The endocannabinoid system, says John Hicks, MD, author of “The Medical Power of Cannabis” is designed to maintain homeostasis in our bodies. “It interconnects all systems, organs and tissues and responds to changes in the internal and external environment,” he writes. “Its whole purpose is to keep our bodies functioning at their best by adapting to change.”
Endocannabinoid receptors exist throughout the brain, playing various functions. For example, CB1 receptors exist in high density in the basal ganglia, helping to control unconscious muscle movements as well as planning and starting movements. There are also CB1 receptors in the amygdala, which influences emotions such as fear and anxiety as well as a high density of receptors in the hippocampus, involved with learning new information and memory integration. Another endocannabinoid receptor CB2 is active in the central nervous system and in present in peripheral tissues and organs, particularly, immune system cells (3). Considering the endocannabinoid system’s biological functions, phytocannabinoids may just be a great thing for your customers not to mention your business.WF
References1. “Establishment of a New Drug Code for Marihuana Extract.” Federal Register. https://www.federalregister.gov/documents/2016/12/14/2016-29941/establishment-of-a-new-drug-code-for-marihuana-extract, Accessed 3/1/2017. 2. E.B. Russo. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.” Br J Pharmacol. 163(7): 1344–1364. 2011. 3. J. Hicks, “The Medical Power of Cannabis.” Skyhorse Publishing. New York. 2015
Published in WholeFoods Magazine April 2017
UPDATED 4/3/2017 9:20am: A previous version of this article referred to Ashley Grace as CEO of CW Hemp when he is in fact CMO.