human body

After such invaluable insight into the U.S. hemp regulations and the 2018 Farm Bill by our very own Joy Beckerman, we return to science in this week’s post. Let’s take a look at some of the different cannabinoids that are found in Cannabis sativa L. and what benefits research on these cannabinoids has revealed.

Now that we are more familiar with the endocannabinoid system, let’s focus on some of the compounds that activate this system and, as of late, have gained a lot of attention—cannabinoids. Becoming familiar with some of the more abundant cannabinoids found in the hemp plant, and the research that has been conducted to further analyze these compounds may help us better understand the effects cannabinoids can have on our systems.

As we have discussed in previous posts, phytocannabinoids are cannabinoids that have been produced in a plant. In this case we are discussing the hemp plant, which as defined by federal regulation cannot contain greater than 0.3% tetrahydrocannabinol (tetra-hydro-cannab-in-al), referred to as THC. THC is just one of over 100 phytocannabinoids¹researchers have discovered within this plant.

“Mother of Cannabinoids”

The highest percentage of phytocannabinoids are found in the unseeded flower buds of female plants.²

The most abundant of the phytocannabinoids begin as “parent” cannabinoids called Cannabigerolic (canna-bi-ger-o-lic) acid or CBGa, also known as the “mother of cannabinoids,” and Cannabigerovarinic acid or CBGVa. The formation of some of the most abundant cannabinoids occurs when CBGa is converted into:

Cannabigerol (canna-bi-ger-al), commonly called CBG;
Cannabidiolic (canna-bi-di-ah-lic) acid—CBDa;
Tetrahydrocannabinolic (tetra-hydro-cannabin-alic) acid—THCa; and
Cannabichromenic (cannabi-chrom-ee-nic) acid—CBCa.

As further break down of these compounds occur other cannabinoids are revealed. In the image below, the parent cannabinoids CBGa and CBGVa, are converted to other compounds.

These chemical conversions typically occur in nature mostly through changes in temperature and time. In the laboratory or manufacturing facility however, these conversions can be achieved in an expedited fashion through a multitude of manufacturing processes such as time, temperature, and pressure. One common example of this process—called decarboxylation (de-carboxil-ation)—involves exposing the plant, or an extract from the plant, to high temperatures over an extended period of time. In a fresh hemp flower or a fresh extract, CBDa exists at a very high level, which can be converted to CBD through the process of decarboxylation, in order to produce products formulated with consistent levels of CBD.

Cannabinoid Benefits

Although discussed less often than CBD, CBG is an important cannabinoid, and like CBD, has been shown to be non-psychotropic (mind-altering).³ In a recent study, CBG was shown to have some aseptic-like properties and activity, and appeared to support the destruction of “drug-resistant MRSA by destroying preformed biofilms and resistant organisms in cell culture and non-human studies.”⁴CBG has also been studied as a possible way to support healthy levels of inflammatory compounds and support normal bone growth and healing.⁵

The acidified compounds of THC and CBD, Tetrahydrocannabinolic acid (THCa) and Cannabidiolic acid (CBDa) are believed to have their own supporting attributes. Like CBG, both THCa and CBDa are non-psychotropic, as they do not produce intoxicating effects. THCa has been researched as a possible way to support healthy cell function and healthy muscle function while CBDa and THCa also have been studied as a way to help support appropriate levels of inflammatory-compounds.⁶ Additionally, in one study, CBDa was correlated with increased serotonin receptor level activation, a receptor associated with the serotonin neurotransmitter, known for its participation in overall well being, emotional balance, and other autonomic system-related functions.⁷

THC, primarily recognized for its psychotropic effects, is used in both medicinal and adult-use forms across the world. The Food and Drug Administration (FDA) has approved three drugs, Marinol^®, Cesamet^®, and Syndros^®, as synthetic versions of THC for therapeutic uses in the United States. As of June 2020, in the U.S., there are over 10 states with adult use regulations and over 30 states with regulations regarding medical use of THC.

CBC, like CBD and CBG, is non-psychotropic, and interestingly, is thought to work through non-cannabinoid receptors that can communicate with the endocannabinoid system (ECS) to help balance emotional fluctuations, support healthy bone growth and support healthy cell function.⁸ Although CBC is structurally similar to THC and CBD, it has been shown to affect the production of our endocannabinoids, leading to an increase in the level of Anandamide. CBC binding appears to take place on capsaicin receptors, called TRPV1, which are responsible for nociception, heat sensation, body temperature, and detection of harmful toxins we ingest or absorb from our external environment.⁹ CBC also binds to sensory receptors, called TRPA1, that stimulate our senses and protective responses¹⁰. Interestingly, studies of CBC use on the skin have shown its support of overall skin health and has shown its ability to maintain normal oil levels.¹¹

Future Cannabinoid Potential

As the science evolves over time, and the variations in the hemp plant continue to change through breeding techniques and genetic research, we will see the potential of many more cannabinoids like Tetrahydryocannabivarin (THCV) and Cannabidivarin (CBDV), which have already begun to show therapeutic potential across multiple body systems. Studies have demonstrated the potential of THCV to support emotional balance, support healthy appetite level and also supports healthy bone growth as studies revealed it binds with both CB1 and CB2 receptors throughout our ECS. ¹² Likewise, CBDV has shown promise in supporting healthy brain development and healthy cellular function by binding with the non-cannabinoid receptor, TRPV1,¹³ previously mentioned as a binding site for CBC. In addition, a few companies have started looking into cultivation of pharma grade, algae-based cannabinoids for medical therapies. With the potentially massive grow ability, algae-based cannabinoids could eliminate the need for synthetic cannabinoids.¹⁴ As many believe the 2018 Farm Bill was passed to create a new stream of income for U.S. farmers, synthetic cannabis and non-hemp derived cannabinoids may become obsolete (i.e. under the guidelines of the U.S. Hemp Authority Certification, synthetic cannabinoids and non-hemp derived cannabinoids are not allowed). We will discuss the ins and outs of the U.S. Hemp Authority in a future post.

For the continued benefit to our bodies and in order to support inner balance, it is important for us to learn more about cannabinoids and to support the research being conducted on these compounds. Although this post discussed the benefits of major cannabinoids in the hemp plant, we did not discuss the most popular one—CBD. Never fear! We didn’t forget it. This cannabinoid is so important, it deserves its own post. In our next post we will take an in-depth look at CBD and the benefits that have been uncovered by past and current research.

Pages: 1 2

Our post this week is brought to you by guest blogger Joy Beckerman, an expert in hemp law and regulations and the new Director of Regulatory and Legal Affairs at Zilis. Joy’s overview of the different States’ regulatory guidelines and contributing Federal factors helps shed light upon how the industry is moving forward and what the industry leaders are doing to ensure access across the country.The dome of the United States capitol with an American flag and dramatic clouds behind

As a preliminary matter, it’s key to understand that just because a Federal law is passed to either partially or fully legalize something, it doesn’t mean that it automatically becomes legal in all 50 States. Under the U.S. Constitution, each of our 50 states wield and maintain political powers held for its own State government rather than Federal government. This is why we see a patchwork of laws and their corresponding regulations across the 50 States on a spectrum of issues.

2014 Farm Bill

After decades of advocacy by dedicated grassroots activists and heroic professionals and legislators who later joined the hemp revolution, a short but significant provision titled, “Legitimacy of Industrial Hemp Research” within the Agricultural Act of 2014 (2014 Farm Bill) was passed; and the amazing hemp crop began to re-establish itself under agricultural pilot programs to study the growth, cultivation, and marketing of industrial hemp in States that enacted laws allowing the cultivation of hemp. The 2014 Farm Bill also defined industrial hemp for the first time in U.S. history, thereby distinguishing it from its Cannabis cousin commonly known as marijuana.

While the 2014 Farm Bill’s introductory words clearly stated, “In General–notwithstanding the Controlled Substances Act…” ¹ —meaning not subject to the Controlled Substances Act—the U.S. Drug Enforcement Administration (DEA) held and publicized the erroneous position for the next four years that hemp extract and cannabinoids derived from hemp were still controlled substances.

The hemp industry was ultimately forced to file a lawsuit against the DEA in the Ninth Circuit Court of Appeals to prove that no part of the hemp plant sown under the provisions of the 2014 Farm Bill, including hemp’s derivatives, extracts, and cannabinoids, were controlled substances. Yet, due to the DEA’s messaging, many States were hesitant to embrace the safe and legal opportunities provided by the agricultural pilot program pathway.

2018 Farm Bill

Learning from all this confusion, hemp industry advocacy organizations and Federal legislators began to carefully and strategically draft expanded hemp provisions in the Agriculture Improvement Act of 2018 (2018 Farm Bill), which was enacted on January 1, 2019. The three most relevant provisions of what we’re seeing among the 50 States’ permissions and regulation—or lack thereof, as the case may be—are as follows:²

Hemp and tetrahydrocannabinols derived from hemp were unequivocally removed from the Controlled Substances Act;
The definition of “hemp” was expanded for total clarity by specifically stating, “The term ‘hemp’ means the plant Cannabis sativa and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.” (Emphasis added.); and
Nothing in the Bill affects or modifies the Federal Food, Drug, and Cosmetic Act.

The final point about the Federal Food, Drug and Cosmetic Act is important for the hemp industry with regard to dietary supplements and food additives. Within the Federal Food, Drug, and Cosmetic Act, a provision commonly referred to as the “Investigational New Drug (IND) Preclusion,” states that if an article has been authorized for investigation for which substantial clinical investigations have been instituted, and made public, then products containing that substance are precluded from the definition of a “dietary supplement” unless it was marketed as a dietary supplement or as a conventional food before new drug investigations were authorized.³

What does this mean? A great example is the use of cannabidiol (CBD) in the approved drug EPIDIOLEX^®. Cannabidiol was submitted as an IND, with substantial clinical investigations made public, and it is currently being debated as to whether CBD can be considered a dietary supplement because no evidence has thus far been identified to demonstrate that CBD was marketed as a dietary supplement before being used in clinical trials to treat specific childhood epilepsy disorders. Regardless of such evidence, this same statute also grants authority to the U.S. Food & Drug Administration (FDA) to override this restriction and simply issue a regulation allowing a substance to be marketed as a dietary supplement that would otherwise be prohibited under the IND Preclusion. The IND Preclusion only applies to dietary supplements and foods and does not apply to cosmetics, thus cosmetics containing CBD are not affected.

The Market

Despite the ongoing debate, the CBD dietary supplement and food markets have grown to such an extent that the Gallup Poll reported in August of 2019 that one in seven [or 14% of] Americans is using a CBD product of some kind.⁴ This has occurred because the FDA’s statements concerning the debate amount only to a guidance position at this point. The FDA’s guidance position has never been determined by the courts to be valid, and is neither final, nor legally binding since no final agency actions or determinations have been issued on the subject. In fact, FDA Commissioner Stephen Hahn recently stated during his address at the National Association of State Departments of Agriculture’s 2020 Winter Policy Conference, “People are using these [CBD] products. We’re not going to be able to say, ‘You can’t use these products,’ because…even if you did, it’s a fool’s game to even try to approach that.”⁵

The hemp industry coalition has been lobbying the FDA to use its overriding authority to allow CBD products to be marketed as dietary supplements and added to food. It has also been providing guidance and safety data to assist the FDA in creating a regulatory framework for quality assurance oversight of hemp processing. The coalition has also been lobbying Congress to mandate these actions, and there is much encouraging movement in these regards.

Challenges Today

In the meantime, and until the FDA formally acts, a mishmash of State laws and regulations govern CBD, with some States only allowing cosmetic CBD products to be sold, and others still not allowing any CBD products to be sold. Conversely, certain States allow all CBD products to be sold with virtually no oversight, while yet others are taking quality assurance into their own hands by creating laws and regulations allowing the sale of all or certain CBD products that are produced in accordance with various testing, labeling, and good manufacturing practices. Some States even have onerous product registration requirements that apply to both in-State and out-of-State manufacturers and distributors.

For the States that do have labeling requirements, these requirements often differ from State to State, making it impossible for national CBD industry leaders to print a single label that complies with all of the various State labeling mandates. One State even requires language that is very similar to, but differs from, FDA-required labeling language, making it impossible to print a label for that State that complies with both State and Federal law.

Yet hemp and its cannabinoids are legal again because we put one foot in front of the other and continue marching this plant down the field. Most State authorities greatly support the CBD industry and do not enforce excessively burdensome requirements. All will eventually come around right and one day we’ll look back on how this critical body of law and regulation unfolded with humor. Stay the course and engage in the process!

[1] Agricultural Act of 2014; H.R. 2642; Pub.L. 113–79, also known as the 2014 Farm Bill

[2] Agriculture Improvement Act of 2018; S. 3042; Pub.L 115-334, also known as the 2018 Farm Bill

[3] §201(ff)(3)(B) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. § 321(ff)(3)(B)]

[4] Jones, J., Saad, L. (2019) Gallup Poll, June 19-July 12, 2019 CBD Consumption Habits [data set] Random sample—2,543—American adults in all 50 states and the District of Columbia. Retrieved from news.gallup.com

[5] YouTube, “FDA Commissioner Hahn makes first public comments on CBD”

Source: https://blog.zilis.com/hemp-vs-marijuana/

Tag: human body

Benefits of Cannabinoids

State Regulatory Overview & Federal Factors