Making Sense of Cannabis Strains Through Chemometrics in Review: Page 4 of 4

April 4, 2019
Volume: 
2
Issue: 
2
Abstract / Synopsis: 

The cannabis industry is constrained by the continued use of acronyms and nonstandard abbreviations for strain naming in lieu of a scientific-based standardized classification convention or lexicon. The rapidly expanding industry is evolving towards an evidence-based model of medicine where cannabis cultivars’ chemical and genotypic profiles can be correlated with sensory perception and pharmacological activities using multivariate analysis. Applying chemometric tools can result in not only the authentication of a given cannabis cultivar but also provide a quality control mechanism for both cannabis flower and any resulting cannabis-based drugs. Using chemometrics on cannabinoid and terpenoid expression data to segregate accessions into clusters provides the initial model on which to support targeted sequencing based on cosegregation of genetic markers associated with key agronomical and pharmacological traits. Such authenticated cannabis products command higher prices at both the wholesale and retail level.

Upside for Cannabis Science

Most of the cannabis-complicit countries regulate cannabis as a medicine. Israel in particular is at least a decade ahead of the U.S. in instituting standardization in the cultivation, extraction, and formulation of cannabis for clinical trials, leading to patentable drugs that will eventually find their way to the U.S. Food and Drug Administration (FDA) for approval and entry into the lucrative prescription drug market in the U.S. Now the U.S. has its neighbor, Canada, not only following in the footsteps of Israel but also legalizing adult use cannabis at the Federal level. U.S. cannabis companies need to play catch up to gain market share, starting with distinguishing cannabis cultivars from the staggering number of named cannabis strains being grown.

 

Steps Toward Standardization

Cannabis strain authentication entails both establishing a strain’s chemoprofile, the chemical composition including cannabinoids and terpenes, if not more, as well as the genotype of the strain, resulting in a fingerprinted signature. Cannabis testing laboratories are the path to strain authentication. Strain authentication is an important step toward development of reliable, consistent whole plant-based medical marijuana and patient consumer confidence, bringing legitimacy to the cannabis industry.

The first step toward standardization in cannabis strain naming would be to throw out the current unregulated model and replace it with the horticultural and agronomic convention of cultivar names. For example, the strain Blue Dream would become Cannabis sativa cv. Blue Dream. The second step would be to associate a referenced chemotype and genotype with Cannabis sativa cv. Blue Dream. The combination of the Blue Dream cultivar name with its chemotype and referenced genotype would authenticate it.

All stakeholders need to participate, from growers to state departments of agriculture to scientists actively working in this area. State regulatory agencies will need to be active participants in creating and overseeing a cannabis registration. There are hopeful signs from the Association of Official Seed Certifying Agencies (AOSCA) with their interest in forming a varietal hemp working group in 2018. In Canada, a plant breeders’ rights certificate was granted to a federally licenced producer for a type I cannabis plant for their variety “MR2017002” (45), adding to the already existing repository for type II hemp varieties currently registered in the country.

As the cannabis industry continues to grow across the U.S. at a rapid pace, the competition amongst growers and producers is also heating up. This competition is reflected in dropping prices at both the wholesale and retail level. There are few options for growers to regain market share in the flooded retail market space. Growers can either cut their costs by engaging testing facilities that provide fewer services and questionable testing results, or they can choose the high road and distinguish their harvests from their competition through authentication of their strains. Authenticated cannabis products command higher prices at both the wholesale and retail level, and the requirement for strain confirmation is an inevitable regulatory requirement.

 

Resulting Utility

Applying chemometric tools to the authentication and quality control of both cannabis flower and cannabis-based drugs can be both efficient and powerful. The efficiency comes from the ability of any cannabis testing laboratory or state reference laboratory to apply standardized analytical methods to obtain phytochemical and genotypic data profiles using more than one analytical method. With the hopeful advent of mandatory cannabis cultivar authentication, cannabis science can advance more readily.

Creating a new lexicon for cannabis cultivars based on scientifically quantifiable values would help to advance cannabis research and commercial cultivation benefiting both regulators and consumers. A new simplified vocabulary that links the chemical makeup of a cannabis cultivar with its olfactory perception could be added to the METRC barcode so that consumers and state regulators know exactly what is being claimed by the cultivator. And verification by specific genotyping would provide the trifecta for cultivar registration. The latter would prove particularly interesting to implement through blockchain technologies for integration into seed to sale tracking programs (46).

Not to be ignored is the sensory perception of the chemical composition of a particular cannabis cultivar and the subconscious or conscious olfactory judgment that is made by the individual cannabis user. We’re just starting to understand how aroma influences one’s discrimination of cannabis and the application of statistical techniques to describe that olfactory experience (9). Future studies linking olfactory perception with chemical profiling, in particular terpenoid profiling, will demonstrate the level of perception already inherent in humans. The vast unknown is what physiological cascade of events that odorant sensation begets.

 

Empowering the Cannabis Industry, Cultivator, Regulator, and Consumer

As the industry rapidly evolves toward big agriculture versus boutique cannabis growers, cannabis cultivar authentication will be a key to success and keeping market share in North America. The cannabis industry must continue its evolution towards an evidence-based model of medicine where cannabis chemical and genotypic profiles need to be correlated with their pharmacological activities using metabolic profiling with multivariate analysis requiring a reoccurring authentication, that is, a certification requirement for cultivators to be in the game.

The current self-inflicted confusion within the U.S. and Canadian cannabis industry is an opportunity to demonstrate scientific ingenuity against the rapidly maturing global cannabis industry, where outdoor growing costs are a fraction of the indoor energy intensive grows. Throwing out unnecessary impediments should be a priority, starting with nonstandard strain naming in favor of the agronomic and horticultural practice of registered “cultivar” names based on full genome sequencing, broad chemometrics, and genotyping to allow for consistent, reproducibly-effective comparisons across the cannabis industry. This will enable trademarking or patenting of specific cultivars.

 

References: 
  1. J. Sawler, J.M. Stout, K.M. Gardner, D. Hudson, J. Vidmar, and L. Butler, et al., PLoS One 10, e0133292. http://dx.doi.org/10.1371/journal.pone.0133292 (2015).
  2. P. Henry, PeerJ PrePrints 3, e1980, doi: 10.7287/peerj.preprints.1553v2 (2015).
  3. R. Lynch, D. Vergara, S. Tittes, K. White, C.J. Schwartz, M.J. Gibbs, T.C. Ruthenburg, K. deCesare, D.P. Land, and N.C. Kane, Crit. Rev. Plant Sci. 35, 349–363, http://dx.doi.org/10.1080/07352689.2016.1265363 (2015).
  4. P. Henry, PeerJ PrePrints 5, e3307v1, https://doi.org/10.7287/peerj.preprints.3307v1 (2017).
  5. C. Dufresnes, C. Jan, F. Bienert, J. Goudet, and L. Fumagalli, PLoS ONE 12(1), e0170522, https://doi.org/10.1371/journal.pone (2017).
  6. K. McKernan, Y. Helbert, V. Tadigotla, S. McLaughlin, J. Spangler, L. Zhang, and D. Smith, bioRxiv doi: https://doi.org/10.1101/028654 (2015).
  7. L. Ericksson, T. Byrne, E. Johansson, J. Trygg, and C. Vikström, Multi- and Megavariate Data Analysis Part 1: Basic Principles and Applications, Second Ed. (Umetrics, Umea, Sweden, 2006).
  8. L. Eriksson, E. Johansson, N. Kettaneh-Wold, J. Tyrgg, C. Wikström, and S. Wold, Multi- and Megavariate Data Analysis Part 1: Basic Principles and Applications, Second Ed. (Umetrics, Umeå, Sweden, 2006).
  9. A. Gilbert and J.A. DiVerdi, PLoS One 13(2), e0192247, https://doi.org/10.1371/journal.pone.0192247 (2018).
  10. D. Sweeney, “Mendocino County divided into cannabis appellations,” North Bay Business Journal (2016).
  11. M. Otto, Chemometrics. Statistics and Computer Application in Analytical Chemistry, (Wiley-VCH, New York, 1998).
  12. Y. Hong, et al., Food Chem. 93, 25–32 (2004).
  13. G. Gurdeniz and B. Ozen, Food Chem. 116, 519–525 (2009).
  14. N.A. Dang, H.G. Janssen, and A.H. Kolk, Bioanalysis 5(24), 3079–3097 (2013).
  15. H.A. Gad, S.H. El-Ahmady, M.I. Abou-Shoer, and M.M. Al-Asisi, Phytochemical Analysis 24(1), 1–24, https://doi.org/10.1002/pca.2378 (2012)
  16. I. Geana, A. Iordache, R. Ionete, A. Marinescu, A. Ranca, and M. Culea, Food Chem. 13, 1125–113 (2013).
  17. A. Hazekamp, K. Tejkalova, and S. Papadimitriou, Cannabis and Cannabinoid Research DOI: 10.1089/can.2016.0017 (2016).
  18. T. Kowalkowski, R. Zbytniewski, J. Szpejna, and B. Buszewski, Water Research 40, 744–752 (2006).
  19. R. Briandet, E.K. Kemsley, and R.H. Wilson, J. Science of Food and Agriculture 71, 359–366 (1996).
  20. L.M. Reid, C.P. O’Donnell, and G. Downey, Trends Food Sci. Technol. 17, 344–353 (2006).
  21. V.E. Tyler, J. Nat. Prod. 62, 1589–15792 (1999).
  22. M.A. Lewis, E.B. Russo, and K.M. Smith, Planta Med. 84, 225–233 (2018).
  23. E. De Meijer, “Cannabis sativa plants rich in cannabichromene and its acid, extracts thereof and methods of obtaining extracts therefrom.” Google Patents, https://www.google.com/patents/US20110098348 (2011).
  24. M.A. Lewis, M.D. Backes, and M. Giese, “Breeding, production, processing and use of specialty cannabis.” Google Patents, https://www.google.com/patents/US9642317 (2015).
  25. M.W. Giese MW and M.A. Lewis, “Systems, apparatuses, and methods for classification.” Google Patents, https://encrypted.google.com/patents/WO2016123160A1?cl=en (2016).
  26. Y. Cohen, “Cannabis plant named ‘avidekel’.” Google Patents, https://www.google.com/patents/US20140259228 (2014).
  27. Y. Cohen, “Cannabis plant named erez.” Google Patents, https://www.google.com/patents/US20140245494 (2014).
  28. Y. Cohen, “Cannabis plant named midnight.” Google Patents, https://www.google.com/patents/US20140245495 (2014).
  29. S.W. Kubby, “Cannabis plant named ‘Ecuadorian Sativa’.” Google Patents, https://www.google.com/patents/USPP27475 (2016).
  30. O. Aizpurua-Olaizola, U. Soydaner, E. Öztürk, D. Schibano, Y. Simsir, P. Navarro, N. Etxebarria, and A. Usobiaga, J. Natural Products 79, 324–331 (2016).
  31. M. Sexton and J. Ziskind, “Sampling cannabis for analytical purposes.” http://liq.wa.gov/publications/Marijuana/BOTEC%20reports/1e-Sampling-Lots-Final.pdf (2013).
  32. D.J. Potter, Drug Testing Anal. 58, S54–S61, http:// dx.doi.org/10.1002/dta15 (2013).
  33. C. Orser, S. Johnson, M. Speck, A. Hilyard, and I. Afia, Natl. Prod. Chem. Res. DOI: 10.4172/2329-6838.1000304 (2017).
  34. Hillig KW (2004) A chemotaxonomic analysis of terpenoid variation in Cannabis. Biochem. Syst. Ecol. 32, 875–891. http://dx.doi.org/10.1016/j.bse.2004.04.004
  35. Hazekamp A, Fischedick JT (2012) Cannabis – from cultivar to chemovar.  Drug Test Anal 4:660–667. http://dx.doi.org/10.1002/dta.407
  36. J.T. Fischedick, A. Hazekamp, T. Erkelens, et al., Phytochemistry 71, 2058–2073 (2010).
  37. E.B. Russo, Frontiers in Pharmacology 7, 1–19 (2016).
  38. B. Russo, Psychopharmacology 165, 431–432 (2003).
  39. E.B. Russo, Br. J. Pharmacology 163, 1344–1364 (2011).
  40. S. Elzinga, J. Fischedick, R. Podkolinski, et al., Nat. Prod. Chem. Res. 3, 1–9 (2015).
  41. G. Buchbaue, in Handbook of Essential Oils:  Science, Technology and Applications, K.H.C. Baser and G. Buchbauer, Eds. (CRC Press, Boca Raton, Florida, 2010) pp. 235–280.
  42. J.K. Booth, J.E. Page, and J. Bohlmann, PLOS One https://doi.org/10.1371/journal.pone.0173911 (2017).
  43. R.E. Schultes, W.M. Klein, T. Plowman, et al., “Cannabis: An Example of Taxonomic Neglect. Botanical Museum Leaflets, Harvard University 23, 337–367 (1974).
  44. S. Johnson, A. Hilyard, P. Henry, S. Tholson, A. Everett, M. Speck, and C. Orser, “Terpenoid Chemoprofiles Distinguish Drug-type Cannabis sativa L. Cultivars in Nevada,” The Emerald Conference (Poster presentation), San Diego, California, 2018.
  45. Medreleaf (2018) MR2017002 http://www.inspection.gc.ca/english/plaveg/pbrpov/cropreport/mari/app00010960e.shtml.
  46. MGC (2018) Blockchained DNA: The Information Chain for Advanced Growers and Regulators, https://cdn2.hubspot.net/hubfs/3402974/Medicinal%20Genomics%20Blockchained%20Cannabis%20DNA.pdf?t=1523386278442&utm_campaign=Validation&utm_source=hs_automation&utm_medium=email&utm_content=57554917&_hsenc=p2ANqtz-_0ukN97Yf_qJtgWnKrkKd8eq7WE5cB7PRwFkfDZqJyNkvtN6HyjpQLrq2EdEYdxA5T8-DybGIGtJiTDz6wlTG8yz0RjgsbQmVxSSscNzkY_pENUgU&_hsmi=57554917
  47. https://phytofacts.info/.
  48. www.chaibio.com/openqpcr.

 

Cindy Orser, PhD, with Digipath Labs in Las Vegas, Nevada. Philippe Henry, PhD, is with VSSL Enterprises in Kelowna, British Columbia, Canada. Direct correspondence to [email protected].

 

How to Cite This Article

C Orser and P Henry, Cannabis Science and Technology 2(2), 38-47 (2019).