Why the Other Molecules Matter

By Christian Poole, Strainprint Technologies Ltd. & Molecular Science Corp.

Whether you call it the “entourage effect”, “ensemble effect,” or you refer to it as an herbal synergy, many cannabis consumers agree that molecules other than THC and CBD have a significant role in the overall effects and experience of consuming cannabis products. Now, a growing body of scientific evidence^1,2,3,4,5,6 is supporting what many cannabis consumers already know – we need to expand our thinking beyond these two major cannabinoids to understand the full spectrum of cannabis effects and how these effects can vary between individuals.

It seems logical that cannabis patients and recreational consumers alike should be provided with the most accurate and fulsome information available about the products they are consuming to derive the most significant benefit and value from these products. Picture this: you are a medical cannabis patient who uses a specific dry flower product to treat symptoms of your medical condition. You have discussed with your medical practitioner about the products that might work best for you and tried a few (maybe several) before finding a product that seemed to alleviate your symptoms. For months, you are using this product and tracking your experiences with the Strainprint App, and achieving successful, reliable management of your symptoms. It feels as if you have found a long-term solution to provide you relief. Then, one day, you go to purchase your same reliable medicine and are told that the product is not in stock. What do you do? Typically, you could look at the label of your preferred product to determine the quantities of active ingredients it contains, then look for a product with similar levels of those active ingredients. For example, if you normally take 200mg daily of generic brand ibuprofen to manage chronic migraine pain, you may decide to purchase name-brand Advil containing 200mg of the same active ingredient per dose. You assume that you will achieve the same efficacy with this alternative product. However, when it comes to finding replacement cannabis products for treating your specific symptoms, the options are not so clearly defined. Patients may find themselves at a loss when seeking a product that will provide them with the same benefits as their usual product, and with no undesired effects.

BACKGROUND

When it comes to phytocannabinoids (plant-derived cannabinoids), THC and CBD are the most commonly known but do not represent the total potential for therapeutic efficacy or consumer experience from cannabis products. A growing body of scientific evidence is showing that lesser-known cannabinoids, such as CBG, CBN, THCV, THCP, while less abundant in common cannabis cultivars, have potential therapeutic value as well and may act synergistically with other compounds in the plant. While the focus of genetic breeding programs in the cannabis industry appears to be the pursuit of cultivars with high levels of THCA/THC or CBDA/CBD, cannabis contains over 500 distinct compounds, including other cannabinoids, terpenes, flavonoids, and omega fatty acids that are relevant to the consumer experience and effects of consuming cannabis.

Terpenes, a class of organic compounds that are primarily responsible for the olfactory and gustatory characteristics of cannabis, have also been linked to its therapeutic effects⁵.  Academic studies have shown that terpenes have diverse physiologic effects and suggest that these compounds may contribute to the observed effects of cannabis². It is with this developing understanding of the full range of chemical constituents in cannabis and their potential benefits that we see a diversification towards the development of cultivars and formulated cannabis products more focused on minor cannabinoids and terpenes. A quick peruse through the Strainprint Community website, a leading platform for the discussion and education surrounding medical cannabis usage, reveals that terpenes are commonly discussed within the medical patient community. The site features several discussion threads about which terpenes are popular among the community and why.

Of late, researchers and medical product developers are starting to look at the potential role of cannflavins in therapeutic cannabis use. This class of compounds was recently brought into the spotlight (specifically Cannflavin A & Cannflavin B) for their anti-inflammatory properties, which research has indicated may be up 30x as potent as common, OTC anti-inflammatory drugs⁷. The potential for compounds with this level of efficacy without the harmful side-effects of other anti-inflammatory drugs is certainly of interest to the medical community.

To date, we know of over 120 cannabinoids, 100+ terpenes, several cannflavins and several other molecules in the cannabis plant with potential therapeutic value or that contribute to a positive consumer experience. Despite this trove of relevant compounds, there is relatively little being done to communicate broader and more accurate information about the chemical profiles of cannabis products to the buyer at the time of purchase.

A REAL WORLD STUDY

For investigational purposes, we decided to dig a bit deeper into the relationship between cannabis products, their chemical profiles, product labels, and reported patient outcomes. Our goal was to demonstrate that two very similarly labelled cannabis products could have significantly different chemical profiles and self-reported efficacy for specific symptoms. To accomplish this, we teamed up with Molecular Science Corp., a leading cannabis product testing company, to analyze chemical profiles of selected cannabis products. In parallel, the Strainprint research team reviewed and provided anonymized patient outcome data collected by the Strainprint App from consumers of these same products.

Products were chosen that had similar product labels (% of total THC/CBD) and a significant number of patient-reported outcomes collected through the Strainprint App. The Strainprint App enables cannabis consumers to record the product they are using, the symptom they are treating, their ‘pre’ medicated score, which is the severity of the symptom (on a scale of 0-10) before consuming their chosen cannabis product, and their ‘post’ medicated score on the same numerical scale. Each patient-reported outcome yields an efficacy score, corresponding to the reduction in the severity of the given symptom.  The Strainprint database holds all of these records and allows products to be assessed in aggregate and assigned an average efficacy score against a particular symptom.

The selected products were procured and submitted to MSC’s lab for analytical testing, specifically for cannabinoid and terpene profiling. The chemical profiles of the two products were then compared to each other and the average efficacy ratings from the Strainprint database. Here is what we found:

Cannabinoids

** Low levels of CBGA were detected in Lab Results in both samples, but all other cannabinoids (CBC, CBDV, CBG, CBM, d8-THC, THCV) were reported as <LOQ which is set at 0.04.

Interestingly, some significant differences were found at the terpene-level (5 largest differences listed of 30 terpenes quantitated):

Terpenes

Next, we dug into the Strainprint data to determine if we could find significant differences in efficacy scores for a specific symptom. In this case, we noted significant differences in average efficacy scores for men < age 45 who consumed these products by inhaling vaporized dried flower for the purpose of relieving joint pain.

Strainprint Efficacy Data

What we see here is that vaping Product A appears to have higher efficacy for treating joint pain in this user group than Product B. Could it be explained by the slightly higher THC levels in Product A? Is it possible that Limonene and Linalool play a role? What if the difference is explained by the total profile of this cultivar and the complex interactions between its chemical constituents and the consumer? While not conclusive in correlating specific chemical differences with different reported efficacy, these results suggest that similarly labelled products can vary significantly in their chemical profiles, and these differences could impact therapeutic value and consumer experience.

COMMENTARY

As cannabis industry professionals are aware, making more detailed and descriptive information on cannabis products available to consumers and medical practitioners is not as simple as we might like. Regulations prevent cannabis producers and product manufacturers from including such information on their product labels or from making claims about a product’s potential medical benefits based on consumer reported data. What can be done? On the one hand, part of the solution lies in the improvement of regulations that will allow this kind of information to be more readily reported, accessed and associated with individual products. On the other hand, some responsibility lies with cannabis producers. Although they are not required to make this information available, it should be part of their efforts to educate and inform cannabis consumers and clinicians. Finally, there is some responsibility that lies with the patients/consumers, whose voices can make an impact on the improvement of both regulations and industry practices. Fortunately, there are existing tools like the StrainPrint App, supported by analytical testing by qualified labs like Molecular Science Corp., that can help consumers and clinicians navigate and evaluate the vast array of cannabis products on the market. These tools can also help the industry to optimize the products they market and empower their customers and patients with accurate, helpful product information.

References

1. Russo, EB. The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain. Front Plant Sci. 2018; 9: 1969
2. Russo, EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharamacol. 2011; 163(7): pp 1344-1364
3. Ferber, S. G., Namdar, D., Hen-Shoval, D., Eger, G., Koltai, H., Shoval, G., Shbiro, L., Weller, A. The “Entourage Effect”: Terpenes Couples with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Current Neuropharmacology. 2020; 18(2): pp 87-96.
4. Koltai, H., Namdar, D. Cannabis Phytomolecule “Entourage”: From Domestication to Medical Use. Trends in Plant Science. 2020; S1360-1385 (20) 30122-9.
5. Baron, E. P. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science. Headache. 2018; 58 (7): pp. 1139-1186
6. LaVigne, J., Hecksel, R., Streicher, J. M. In Defense of the “Entourage Effect”: Terpenes Found in Cannabis sativa Activate the Cannabinoid Receptor 1 In Vivo. FASEB. 2020; 34(s1)
7. Barrett, M. L., Gordon, G., Evans, F. J. Isolation from Cannabis sativa L. of cannflavin – a novel inhibitor of prostaglandin production. Biochem. Pharmacol. 1985; (34) pp. 2019-2024.