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 states2,3, 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.
- Turner SE et al. “Molecular pharmacology of phytocannabinoids.” Progress in the Chemistry of Organic Natural Products, vol. 103 (2017): 61-101
- Borrelli F et al. “Beneﬁcial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inﬂammatory bowel disease.” Biochemical Pharmacology, vol. 85, no. 9 (May 1, 2013): 1306-1316
- Wirth PW et al. “Anti-inflammatory properties of cannabichromene.” Life Sciences, vol. 26, no. 23 (June 9, 1980): 1991-1995
- Yoshida H et al. “Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives.” Chemical & Pharmaceutical Bulletin, vol. 43, no. 2 (February 1995): 335-337
- 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
- Ruth G et al. “Overcoming the bell‐shaped dose‐response of cannabidiol by using cannabis extract enriched in cannabidiol.” Pharmacology & Pharmacy. Published online February 2015.
- Wagner H et al. “Synergy research: approaching a new generation of phytopharmaceuticals.” Phytomedicine, vol. 16, no. 2-3 (March 2009): 97–110
- Liu RH. “Health-promoting components of fruits and vegetables in the diet.” Advances in Nutrition, vol. 4, no. 3 (May 1, 2013): 384S–392S
- Eﬀerth T et al. “Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.” Current Drug Targets, vol. 12, no. 1 (January 2011): 122-132