Beyond CBD: Other cannabinoids in hemp and their exciting potential as ingredients

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With the hemp-derived cannabinoid cannabidiol (CBD) enjoying widespread public interest and acceptance as a compound that exhibits a range of health benefits, a major question remains: What’s next? To date, consumer interest in cannabis-derived ingredients has centered on the most abundant “major” cannabinoids in the cannabis flower: CBD and tetrahydrocannabinol (THC). (THC is the psychoactive ingredient in marijuana.) However, with more than 120 other naturally occurring cannabinoids known to exist in the hemp plant (Cannabis sativa)¹, the potential for these other molecules as dietary supplement ingredients is nearly endless. In fact, the full range of cannabinoids has yet to be explored both scientifically and by consumers.

Recent interest in hemp-derived ingredients has begun to shift to the “minor” cannabinoids cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN). The newfound interest in these cannabinoids is likely a result of their relative abundance in the plant and ease of access compared to many of the rarer cannabinoids. CBG, CBC, and CBN are the next most common cannabinoids in cannabis after CBD and THC, and as such the only molecules currently feasible to begin using in nutraceuticals.

A wealth of anecdotal information on these minor cannabinoids can be found on the internet, but unfortunately very little of this information is supported by rigorous scientific research to date. Some studies have implicated CBG and CBC in the treatment of inflammatory disease states^2,3, and CBN has been implicated-though weakly-as a potential sleep aid.⁴

Findings from individual studies like these certainly do not form a basis for medical treatments or other health uses, but the National Institutes of Health (NIH) has acknowledged the beneficial health potential of these molecules, recently announcing R21 grants (“intended to encourage exploratory/developmental research by providing support for the early and conceptual stages of project development”) for the study of the effects of these cannabinoids (and others) as they relate to pain treatment.⁵

As more rigorous scientific study is allowed, funded, and performed, the potential of hemp-derived cannabinoids outside of just CBD is massive. The rest of this article will highlight the three most exciting avenues of product development for manufacturers looking to work with a wider range of cannabinoids, as well as the challenges that remain.

Opportunity #1: Full-Spectrum Products

The first illustration of the potential of working with a broader range of cannabinoids outside of just CBD is “full-spectrum” products and their widely discussed “entourage effect.” The entourage effect is a phenomena that has been cited in a handful of scientific papers and boils down to the notion that a mixture of cannabinoids works better, or differently, than a single cannabinoid in isolation.^6,7 These findings are not inherently shocking. Many plant extracts containing a mixture of molecules are known to work synergistically with more potent effects, compared to individual isolated compounds in these same extracts.^8,9 Minor cannabinoids in hemp extracts, for instance, may play an important role in these synergistic, full-spectrum products.

Even as the popularity of full-spectrum products grows, there is still a lot we don’t know about their effects. Though the entourage effect has been scientifically documented, claims of efficacy online far outpace the supportive science. In the case of CBD, the primary study validating these claims is a study treating mice suffering from inflammation.⁶ The study authors noted that CBD isolate (a pure formulation of the individual cannabinoid) exhibited a bell-shaped dose response-i.e., a certain dosage demonstrated maximum efficacy, and increasing dosages actually had diminishing medicinal effects. In contrast, it was observed that mice treated with a “full-spectrum” extract, which included the cannabinoids CBD, THC, CBG, CBC, and CBN, plus terpenes and other plant molecules, experienced increasing medicinal effects as the dose increased, corresponding to a linear increase in efficacy as compared to the bell-shaped response from pure CBD isolate.

It is not possible from this study alone to discern which constituents of the “full-spectrum” extract were responsible for the increased efficacy. Perhaps the CBG present in the extract was solely responsible for the effect, or perhaps the combination of CBG and CBC with CBD was important. Or maybe it was just the CBC itself. Any claims made online about the nature of the effect seen in this study surmising which molecules were responsible for efficacy have yet to be fully scientifically validated.

Moving forward, it will be important to not only study the effects of individual cannabinoids, but to study mixtures of cannabinoids and terpenes in a controlled and scientific fashion. This simply has not been done to date. Full-spectrum extracts as ingredients may truly have different or greater medicinal effects, but current claims should be treated as anecdotal at best.

Along with the difficulties in producing THC-free full-spectrum extracts, another challenge is that there is a myriad of misinformation and debate about what full-spectrum actually means. Unfortunately, there is currently no widely accepted definition of full-spectrum. Some individuals claim that all cannabinoids, including THC, must be present in a true full-spectrum extract, while others claim that only CBD and terpenes must be present. Still others claim that a diluted extract-with THC, CBG, and CBC present at levels below 0.3% or at undetectable levels-is still considered full-spectrum. For now, manufacturers and consumers have to decide on their own accepted definition. Manufacturers sourcing or offering a “full-spectrum” extract should therefore be knowledgeable about the minor cannabinoid and terpene content of their product.

Opportunity #2: Formulating with Select “Minor” Cannabinoid Isolates

Given the current complexities pertaining to full-spectrum extracts, some manufacturers may find it useful to consider formulating with specific “minor” cannabinoids. As mentioned above, the current understanding of the medicinal effects of these minor cannabinoids is sparse, and this area of research is still in its infancy. However, one can imagine the exciting future opportunities to create nutraceuticals as the understanding of how these cannabinoids work is further developed. Unique formulations created with mixtures of cannabinoids could provide different health benefits, especially when formulated together in a controlled fashion.

For instance, CBG and CBC isolates are becoming available in the marketplace and represent an exciting formulating opportunity. With these and other isolates, formulators can begin to tinker with new ratios of cannabinoids, creating truly unique cannabinoid mixtures. It is easy to picture a nearly infinite variety of cannabinoid-rich products tailored for specific health effects. Examples of this could include a 1:1 ratio of two cannabinoids in a tincture (e.g., 500 mg of CBD and 500 mg of CBG). Alternatively, a product with three cannabinoids at different ratios could be formulated, such as a lotion with 30% CBD, 15% CBC, and 5% CBG.

The ability to play with the cannabinoid ratio “lever” is one of the most exciting and powerful tools formulators have, especially as new technologies enable the isolation of more and more cannabinoids. Aside from the ability to make highly standardized cannabinoid products using isolates (something that is impossible when using raw hemp extracts and unprocessed full-spectrum oil), isolates offer the additional benefit of enabling a high content of minor cannabinoids in end consumer products while avoiding the legal troubles encountered when formulating with extracts or distillates that contain high quantities of THC.

Opportunity #3: High-Potency Full-Spectrum Cannabinoid Powders

Though it is widely assumed that the only way to capture the benefits of the entourage effect is through full-spectrum hemp extracts and distillates in their crude oil form, recently, full-spectrum powders have begun hitting the marketplace. This unique product format offers many of the benefits of full-spectrum products, including the opportunity to work with a wider variety of cannabinoids, while avoiding the processing and manufacturing difficulties encountered when working with highly variable and viscous full-spectrum hemp extracts or distillates. High-potency cannabinoid powders can be formulated with both major and minor cannabinoids, and also contain terpenes and other phytochemicals from hemp. When thinking of exciting opportunities for manufacturers trying to expand past the standard CBD products on the market today, the ease of production and standardization enabled by full-spectrum powders makes them worth specifically focusing on.

Crude hemp extracts and distillates are notoriously cumbersome to work with because of their highly viscous and “sticky” nature. In formulators’ hands, these often clog equipment, stick to processing machinery, and create a general mess. To avoid these problems, formulators are forced to work with the extracts and distillates at high temperatures, which has been shown to degrade valuable cannabinoid material over time, especially in the presence of oxygen.

High-potency cannabinoid powders, on the other hand, provide a great platform for formulators because they can be processed at room temperature, avoiding cannabinoid decomposition, and with all the equipment commonly used in the industry to handle powdered ingredients.

High-potency cannabinoid powders contain specific ratios of cannabinoids-as well as the terpenes, fatty acids, and proteins from hemp extracts-and can be used to easily formulate a host of products, including: lotions, baked goods, tinctures, and water-soluble formulations. Additionally, though high-potency cannabinoid powders often contain high percentages of CBD, a formulator does not have to worry about the “crash-out” problem encountered when using distillates with similarly high levels of CBD. (The “crash-out” problem occurs when CBD distillates with greater than ~50% CBD form crystals in the oil, leading to inconsistent and heterogenous formulations, as well as crystal blockages in processing equipment). A final benefit of high-potency cannabinoid powders is that, similar to cannabinoid isolates, they can be made completely THC free.

Endless Possibilities

With the recent explosion of the CBD market, it is an exciting time to be a nutraceutical manufacturer working with hemp-derived ingredients. The new avenues of working with THC-free ingredients that contain high concentrations of minor cannabinoids outlined above are just a few of the most exciting breakthroughs in the market to date.

As the science behind the health benefits of the individual cannabinoids and cannabinoid mixtures develops, the market is ripe for a plethora of new products. With consumer awareness and acceptance of the true medicinal benefits to be gained from cannabis at an all-time high, there has never been a better time for product formulators and manufacturers to start working with hemp-derived ingredients.

Jake Black, PhD is a co-founder of Treehouse (https://treehousehemp.com/), a supplier of cannabinoid ingredients, and serves as the company’s chief scientific officer (CSO). As CSO, he heads a team of chemists working to lead the industry in cannabinoid isolation and formulation. Jake obtained his PhD in Organic Chemistry from Yale University as an NSF Graduate Research Fellow, and his B.S. in Chemistry with Honors from Villanova University. Jake’s research focused on medicinal chemistry and the development of new spectroscopic methods, fields in which he has authored multiple papers. For more of this thought leadership, connect with him on LinkedIn at https://www.linkedin.com/in/jacob-black-phd-32862126/.

References:

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5. National Institutes of Health. Department of Health and Human Service. Part 1. Overview Information. https://grants.nih.gov/grants/guide/rfa-files/rfa-at-19-009.html
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